International Journal of Molecular Sciences

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24 pages, 10096 KiB

Open AccessArticle

Acral Melanoma Is Infiltrated with cDC1s and Functional Exhausted CD8 T Cells Similar to the Cutaneous Melanoma of Sun-Exposed Skin

by Saraí G. De Leon-Rodríguez, Cristina Aguilar-Flores, Julián A. Gajón, Alejandra Mantilla, Raquel Gerson-Cwilich, José Fabián Martínez-Herrera, Benigno E. Rodríguez-Soto, Claudia T. Gutiérrez-Quiroz, Vadim Pérez-Koldenkova, Samira Muñoz-Cruz, Laura C. Bonifaz and Ezequiel M. Fuentes-Pananá

Int. J. Mol. Sci. 2023, 24(5), 4786; https://doi.org/10.3390/ijms24054786 - 1 Mar 2023

Cited by 1 | Viewed by 3074

Abstract

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel [...] Read more.

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1⁺) CD8 T cells and PD-1 ligand (PD-L1⁺) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells’ capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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14 pages, 4319 KiB

Open AccessArticle

Structural Basis of the Binding Mode of the Antineoplastic Compound Motixafortide (BL-8040) in the CXCR4 Chemokine Receptor

by Mariana Rebolledo-Bustillo, David Garcia-Gomez, Eliud Morales Dávila, María Eugenia Castro, Norma A. Caballero, Francisco J. Melendez, Victor M. Baizabal-Aguirre, Brenda L. Sanchez-Gaytan and Jose Manuel Perez-Aguilar

Int. J. Mol. Sci. 2023, 24(5), 4393; https://doi.org/10.3390/ijms24054393 - 23 Feb 2023

Cited by 7 | Viewed by 2667

Abstract

Modulation of the CXCL12–CXCR4 signaling axis is of the utmost importance due to its central involvement in several pathological disorders, including inflammatory diseases and cancer. Among the different currently available drugs that inhibit CXCR4 activation, motixafortide—a best-in-class antagonist of this GPCR receptor—has exhibited [...] Read more.

Modulation of the CXCL12–CXCR4 signaling axis is of the utmost importance due to its central involvement in several pathological disorders, including inflammatory diseases and cancer. Among the different currently available drugs that inhibit CXCR4 activation, motixafortide—a best-in-class antagonist of this GPCR receptor—has exhibited promising results in preclinical studies of pancreatic, breast, and lung cancers. However, detailed information on the interaction mechanism of motixafortide is still lacking. Here, we characterize the motixafortide/CXCR4 and CXCL12/CXCR4 protein complexes by using computational techniques including unbiased all-atom molecular dynamics simulations. Our microsecond-long simulations of the protein systems indicate that the agonist triggers changes associated with active-like GPCR conformations, while the antagonist favors inactive conformations of CXCR4. Detailed ligand–protein analysis indicates the importance of motixafortide’s six cationic residues, all of which established charge–charge interactions with acidic CXCR4 residues. Furthermore, two synthetic bulky chemical moieties of motixafortide work in tandem to restrict the conformations of important residues associated with CXCR4 activation. Our results not only elucidate the molecular mechanism by which motixafortide interacts with the CXCR4 receptor and stabilizes its inactive states, but also provide essential information to rationally design CXCR4 inhibitors that preserve the outstanding pharmacological features of motixafortide. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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12 pages, 2277 KiB

Open AccessArticle

A Novel Combination of Sotorasib and Metformin Enhances Cytotoxicity and Apoptosis in KRAS-Mutated Non-Small Cell Lung Cancer Cell Lines through MAPK and P70S6K Inhibition

by Pedro Barrios-Bernal, José Lucio-Lozada, Maritza Ramos-Ramírez, Norma Hernández-Pedro and Oscar Arrieta

Int. J. Mol. Sci. 2023, 24(5), 4331; https://doi.org/10.3390/ijms24054331 - 22 Feb 2023

Cited by 3 | Viewed by 3227

Abstract

Novel inhibitors of KRAS with G12C mutation (sotorasib) have demonstrated short-lasting responses due to resistance mediated by the AKT-mTOR-P70S6K pathway. In this context, metformin is a promising candidate to break this resistance by inhibiting mTOR and P70S6K. Therefore, this project aimed to explore [...] Read more.

Novel inhibitors of KRAS with G12C mutation (sotorasib) have demonstrated short-lasting responses due to resistance mediated by the AKT-mTOR-P70S6K pathway. In this context, metformin is a promising candidate to break this resistance by inhibiting mTOR and P70S6K. Therefore, this project aimed to explore the effects of the combination of sotorasib and metformin on cytotoxicity, apoptosis, and the activity of the MAPK and mTOR pathways. We created dose–effect curves to determine the IC50 concentration of sotorasib, and IC10 of metformin in three lung cancer cell lines; A549 (KRAS G12S), H522 (wild-type KRAS), and H23 (KRAS G12C). Cellular cytotoxicity was evaluated by an MTT assay, apoptosis induction through flow cytometry, and MAPK and mTOR pathways were assessed by Western blot. Our results showed a sensitizing effect of metformin on sotorasib effect in cells with KRAS mutations and a slight sensitizing effect in cells without K-RAS mutations. Furthermore, we observed a synergic effect on cytotoxicity and apoptosis induction, as well as a notable inhibition of the MAPK and AKT-mTOR pathways after treatment with the combination, predominantly in KRAS-mutated cells (H23 and A549). The combination of metformin with sotorasib synergistically enhanced cytotoxicity and apoptosis induction in lung cancer cells, regardless of KRAS mutational status. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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12 pages, 2754 KiB

Open AccessArticle

Expression of DNA Methyltransferase 3B Isoforms Is Associated with DNA Satellite 2 Hypomethylation and Clinical Prognosis in Advanced High-Grade Serous Ovarian Carcinoma

by Victor M. Del Castillo Falconi, José Díaz-Chávez, Karla Torres-Arciga, Fernando Luna-Maldonado, Adriana A. Gudiño-Gomez, Abraham Pedroza-Torres, Clementina Castro-Hernández, David Cantú de León and Luis A. Herrera

Int. J. Mol. Sci. 2022, 23(21), 12759; https://doi.org/10.3390/ijms232112759 - 22 Oct 2022

Cited by 3 | Viewed by 2627

Abstract

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on [...] Read more.

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on catalytic activity. Abnormal expression of DNMT3B isoforms is frequently observed in several types of cancer, such as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma. However, the expression patterns and consequences of DNMT3B isoforms in OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms expression by qPCR in 63 OC samples and their association with disease-free survival (DFS), overall survival (OS), and tumor progression. We included OC patients with the main histological subtypes of EOC and patients in all the disease stages and found that DNMTs were overexpressed in advanced stages (p-value < 0.05) and high-grade OC (p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in advanced stages (p-value = 0.0251) and high-grade serous ovarian carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004) serous ovarian carcinoma (SOC). Finally, we observed that overexpression of DNMT3B isoforms was associated with poor prognosis in OC and SOC. DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value = 0.038) in SOC patients. In addition, the ovarian carcinoma cell lines OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2 sequences in the pericentromeric region. In summary, our results suggest that DNMT3B3 expression is altered in OC. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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20 pages, 3297 KiB

Open AccessArticle

The Transcriptomic Landscape of Pediatric Astrocytoma

by Abrahan Hernández-Hernández, Tayde López-Santaella, Aranxa Torres-Caballero, Amarantha Serrato, Ulises Torres-Flores, Diego Montesinos-Valencia, Fernando Chico-Ponce de León, Vicente González-Carranza, Samuel Torres-García, Rosa Rebollar-Vega, Inti Alberto De la Rosa-Velázquez, Rosario Ortiz, Monserrat Pérez-Ramírez, Normand García-Hernández, Antonio García-Méndez and Francisco Arenas-Huertero

Int. J. Mol. Sci. 2022, 23(20), 12696; https://doi.org/10.3390/ijms232012696 - 21 Oct 2022

Cited by 5 | Viewed by 2759

Abstract

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are [...] Read more.

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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15 pages, 2641 KiB

Open AccessArticle

Pancreatic Cancer Cells Induce MicroRNA Deregulation in Platelets

by Jorge Yassen Díaz-Blancas, Ismael Dominguez-Rosado, Carlos Chan-Nuñez, Jorge Melendez-Zajgla and Vilma Maldonado

Int. J. Mol. Sci. 2022, 23(19), 11438; https://doi.org/10.3390/ijms231911438 - 28 Sep 2022

Cited by 2 | Viewed by 2209

Abstract

Pancreatic cancer is a pathology with a high mortality rate since it is detected at advanced stages, so the search for early-stage diagnostic biomarkers is essential. Liquid biopsies are currently being explored for this purpose and educated platelets are a good candidate, since [...] Read more.

Pancreatic cancer is a pathology with a high mortality rate since it is detected at advanced stages, so the search for early-stage diagnostic biomarkers is essential. Liquid biopsies are currently being explored for this purpose and educated platelets are a good candidate, since they are known to present a bidirectional interaction with tumor cells. In this work, we analyzed the effects of platelets on cancer cells’ viability, as determined by MTT, migration using transwell assays, clonogenicity in soft agar and stemness by dilution assays and stem markers’ expression. We found that the co-culture of platelets and pancreatic cancer cells increased the proliferation and migration capacity of BXCP3 cells, augmented clonogenicity and induced higher levels of Nanog, Sox2 and Oct4 expression. As platelets can provide horizontal transfer of microRNAs, we also determined the differential expression of miRNAs in platelets obtained from a small cohort of pancreatic cancer patients and healthy subjects. We found clear differences in the expression of several miRNAs between platelets of patients with cancer healthy subjects. Moreover, when we analyzed microRNAs from the platelets of the pancreatic juice and blood derived from each of the cancer patients, interestingly we find differences between the blood- and pancreatic juice-derived platelets suggesting the presence of different subpopulations of platelets in cancer patients, which warrant further analysis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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10 pages, 1817 KiB

Open AccessCommunication

Epidemiology of Breast Cancer in Mexican Women with Obesity as a Risk Factor

by Shaila Cejudo-Arteaga, Miguel Ángel Guerrero-Ramos, Roberto Kuri-Exome, Erika Martínez-Cordero, Felipe Farias-Serratos and María Maldonado-Vega

Int. J. Mol. Sci. 2022, 23(18), 10742; https://doi.org/10.3390/ijms231810742 - 15 Sep 2022

Cited by 1 | Viewed by 2717

Abstract

Purpose. Adipose tissue in overweight and obesity shows metabolic imbalance in the function of adipocytes and macrophages, this leads to altered regulation of hunger, lipid storage, and chronic inflammation possibly related to the development of breast cancer. Methods. The study was [...] Read more.

Purpose. Adipose tissue in overweight and obesity shows metabolic imbalance in the function of adipocytes and macrophages, this leads to altered regulation of hunger, lipid storage, and chronic inflammation possibly related to the development of breast cancer. Methods. The study was retrospective of 653 breast cancer patients treated at a tertiary care hospital. Histopathology, hormone receptors, grade, clinical stage, clinical biometry analysis, CEA and CA 15-3 antigens were analyzed. The analyses were performed at diagnosis and at the end of oncological treatments. Results. Mexican women studied and treated for breast cancer have an BMI of 29 from diagnosis and at the end of their cancer treatments. The average age was 52 ± 12 years, 54% in women older than 55 years. Cancer recurrence occurs in any molecular type; however, the common factor was overweight and obesity with 73% vs. 21% in normal weight patients. The most frequent tumor tissue in the population was positive hormone receptors of the luminal type (65%), HER2 (15%), and NT (15%). The analyses of macrophages/lymphocytes (M/L), CEA, and CA 15-3 antigens evaluated in women >55 and <55 years, with and without recurrence are elevated at the end of oncological treatments. Conclusions. The analysis of Mexican women with breast cancer showed a predominance of overweight and obesity at diagnosis and at the end of treatment. A relationship between obesity and cancer recurrence with a low response to treatment due to elevation in Ag CEA and CA 15-3 is suggested. The L/M ratio could be an indicator of inflammation related to adipose tissue since diagnosis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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15 pages, 2941 KiB

Open AccessArticle

Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients

by Daniel Martínez-Anaya, Dafné Moreno-Lorenzana, Adriana Reyes-León, Ulises Juárez-Figueroa, Michael Dean, María Montserrat Aguilar-Hernández, Netzi Rivera-Sánchez, Jessica García-Islas, Victoria Vieyra-Fuentes, Marta Zapata-Tarrés, Luis Juárez-Villegas, Rogelio Paredes-Aguilera, Lourdes Vega-Vega, Roberto Rivera-Luna, María del Rocío Juárez-Velázquez and Patricia Pérez-Vera

Int. J. Mol. Sci. 2022, 23(17), 9587; https://doi.org/10.3390/ijms23179587 - 24 Aug 2022

Cited by 10 | Viewed by 2937

Abstract

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano–Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse [...] Read more.

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano–Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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18 pages, 2971 KiB

Open AccessArticle

c-Kit Induces Migration of Triple-Negative Breast Cancer Cells and Is a Promising Target for Tyrosine Kinase Inhibitor Treatment

by José A. López-Mejía, Luis F. Tallabs-Utrilla, Pablo Salazar-Sojo, Jessica C. Mantilla-Ollarves, Manuel A. Sánchez-Carballido and Leticia Rocha-Zavaleta

Int. J. Mol. Sci. 2022, 23(15), 8702; https://doi.org/10.3390/ijms23158702 - 5 Aug 2022

Cited by 14 | Viewed by 3231

Abstract

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and the absence of targeted therapy. c-Kit, a receptor tyrosine kinase (RTK), is considered a molecular target for anticancer drugs. Tyrosine kinase inhibitors (TKIs) recognizing c-Kit are used for the treatment of c-Kit-expressing [...] Read more.

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and the absence of targeted therapy. c-Kit, a receptor tyrosine kinase (RTK), is considered a molecular target for anticancer drugs. Tyrosine kinase inhibitors (TKIs) recognizing c-Kit are used for the treatment of c-Kit-expressing tumors. However, the expression, function, and therapeutic potential of c-Kit have been little explored in TNBC. Here, we studied the expression and effects of c-Kit in TNBC through in vitro and in silico analysis, and evaluated the response to TKIs targeting c-Kit. Analysis of TNBC cells showed the expression of functional c-Kit at the cell membrane. The stimulation of c-Kit with its ligand induced the activation of STAT3, Akt, and ERK1/2, increasing cell migration, but had no effect on cell proliferation or response to Doxorubicin. Analysis of public datasets showed that the expression of c-Kit in tumors was not associated with patient survival. Finally, TNBC cells were susceptible to TKIs, in particular the effect of Nilotinib was stronger than Doxorubicin in all cell lines. In conclusion, TNBC cells express functional c-Kit, which is a targetable molecule, and show a strong response to Nilotinib that may be considered a candidate drug for the treatment of TNBC. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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15 pages, 3278 KiB

Open AccessArticle

Allopregnanolone Promotes Migration and Invasion of Human Glioblastoma Cells through the Protein Tyrosine Kinase c-Src Activation

by Carmen J. Zamora-Sánchez, Claudia Bello-Alvarez, Mauricio Rodríguez-Dorantes and Ignacio Camacho-Arroyo

Int. J. Mol. Sci. 2022, 23(9), 4996; https://doi.org/10.3390/ijms23094996 - 30 Apr 2022

Cited by 5 | Viewed by 2268

Abstract

Glioblastomas (GBs) are the most aggressive and common primary malignant brain tumors. Steroid hormone progesterone (P4) and its neuroactive metabolites, such as allopregnanolone (3α-THP) are synthesized by neural, glial, and malignant GB cells. P4 promotes cellular proliferation, migration, and invasion of human GB [...] Read more.

Glioblastomas (GBs) are the most aggressive and common primary malignant brain tumors. Steroid hormone progesterone (P4) and its neuroactive metabolites, such as allopregnanolone (3α-THP) are synthesized by neural, glial, and malignant GB cells. P4 promotes cellular proliferation, migration, and invasion of human GB cells at physiological concentrations. It has been reported that 3α-THP promotes GB cell proliferation. Here we investigated the effects of 3α-THP on GB cell migration and invasion, the participation of the enzymes involved in its metabolism (AKR1C1-4), and the role of the c-Src kinase in 3α-THP effects in GBs. 3α-THP 100 nM promoted migration and invasion of U251, U87, and LN229 human-derived GB cell lines. We observed that U251, LN229, and T98G cell lines exhibited a higher protein content of AKR1C1-4 than normal human astrocytes. AKR1C1-4 silencing did not modify 3α-THP effects on migration and invasion. 3α-THP activated c-Src protein at 10 min (U251 cells) and 15 min (U87 and LN229 cells). Interestingly, the pharmacological inhibition of c-Src decreases the promoting effects of 3α-THP on cell migration and invasion. Together, these data indicate that 3α-THP promotes GB migration and invasion through c-Src activation. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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10 pages, 1688 KiB

Open AccessArticle

Detection of Myosin 1g Overexpression in Pediatric Leukemia by Novel Monoclonal Antibodies

by Rosa Isela Rodríguez-Téllez, Rosa María Ribas-Aparicio and Genaro Patiño-López

Int. J. Mol. Sci. 2022, 23(7), 3912; https://doi.org/10.3390/ijms23073912 - 1 Apr 2022

Viewed by 2050

Abstract

Myosin 1g (Myo1g) is a mechanoenzyme associated with actin filaments, expressed exclusively in hematopoietic cells, and involved in various cellular functions, including cell migration, adhesion, and membrane trafficking. Despite the importance of Myo1g in distinct functions, there is currently no monoclonal antibody (mAb) [...] Read more.

Myosin 1g (Myo1g) is a mechanoenzyme associated with actin filaments, expressed exclusively in hematopoietic cells, and involved in various cellular functions, including cell migration, adhesion, and membrane trafficking. Despite the importance of Myo1g in distinct functions, there is currently no monoclonal antibody (mAb) against Myo1g. mAbs are helpful tools for the detection of specific antigens in tumor cells and other tissues. The development of mAbs against targeted dysregulated molecules in cancer cells remains a crucial tool for aiding in the diagnosis and the treatment of patients. Using hybridoma technology, we generated a panel of hybridomas specific for Myo1g. ELISA, immunofluorescence, and Western blot assay results revealed the recognition of Myo1g by these novel monoclonal antibodies in normal and transformed T and B cells. Here, we report the development and application of new monoclonal antibodies against Myo1g for their potential use to detect its overexpression in acute lymphoblastic leukemia (ALL) patients. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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Review

Jump to: Research

17 pages, 3882 KiB

Open AccessReview

Mexican Colorectal Cancer Research Consortium (MEX-CCRC): Etiology, Diagnosis/Prognosis, and Innovative Therapies

by Antonio Andrade-Meza, Luis E. Arias-Romero, Leonel Armas-López, Federico Ávila-Moreno, Yolanda I. Chirino, Norma L. Delgado-Buenrostro, Verónica García-Castillo, Emma B. Gutiérrez-Cirlos, Imelda Juárez-Avelar, Sonia Leon-Cabrera, Mónica G. Mendoza-Rodríguez, Jonadab E. Olguín, Araceli Perez-Lopez, Carlos Pérez-Plasencia, José L. Reyes, Yesennia Sánchez-Pérez, Luis I. Terrazas, Felipe Vaca-Paniagua, Olga Villamar-Cruz and Miriam Rodríguez-Sosa

Int. J. Mol. Sci. 2023, 24(3), 2115; https://doi.org/10.3390/ijms24032115 - 20 Jan 2023

Cited by 3 | Viewed by 2929

Abstract

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores [...] Read more.

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores Iztacala from the Universidad Nacional Autónoma de México (UNAM) established an intramural consortium that involves a multidisciplinary group of researchers, technicians, and postgraduate students to contribute to the understanding of this pathology in Mexico. This article is about the work developed by the Mexican Colorectal Cancer Research Consortium (MEX-CCRC): how the Consortium was created, its members, and its short- and long-term goals. Moreover, it is a narrative of the accomplishments of this project. Finally, we reflect on possible strategies against CRC in Mexico and contrast all the data presented with another international strategy to prevent and treat CRC. We believe that the Consortium’s characteristics must be maintained to initiate a national strategy, and the reported data could be useful to establish future collaborations with other countries in Latin America and the world. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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21 pages, 4172 KiB

Open AccessReview

Allopregnanolone: Metabolism, Mechanisms of Action, and Its Role in Cancer

by Carmen J. Zamora-Sánchez and Ignacio Camacho-Arroyo

Int. J. Mol. Sci. 2023, 24(1), 560; https://doi.org/10.3390/ijms24010560 - 29 Dec 2022

Cited by 8 | Viewed by 5015

Abstract

Allopregnanolone (3α-THP) has been one of the most studied progesterone metabolites for decades. 3α-THP and its synthetic analogs have been evaluated as therapeutic agents for pathologies such as anxiety and depression. Enzymes involved in the metabolism of 3α-THP are expressed in classical and [...] Read more.

Allopregnanolone (3α-THP) has been one of the most studied progesterone metabolites for decades. 3α-THP and its synthetic analogs have been evaluated as therapeutic agents for pathologies such as anxiety and depression. Enzymes involved in the metabolism of 3α-THP are expressed in classical and nonclassical steroidogenic tissues. Additionally, due to its chemical structure, 3α-THP presents high affinity and agonist activity for nuclear and membrane receptors of neuroactive steroids and neurotransmitters, such as the Pregnane X Receptor (PXR), membrane progesterone receptors (mPR) and the ionotropic GABA_A receptor, among others. 3α-THP has immunomodulator and antiapoptotic properties. It also induces cell proliferation and migration, all of which are critical processes involved in cancer progression. Recently the study of 3α-THP has indicated that low physiological concentrations of this metabolite induce the progression of several types of cancer, such as breast, ovarian, and glioblastoma, while high concentrations inhibit it. In this review, we explore current knowledge on the metabolism and mechanisms of action of 3α-THP in normal and tumor cells. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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18 pages, 1009 KiB

Open AccessReview

The Role of microRNAs in the Gonocyte Theory as Target of Malignancy: Looking for Potential Diagnostic Biomarkers

by Fabiola García-Andrade, Rosa María Vigueras-Villaseñor, Margarita Dolores Chávez-Saldaña, Julio César Rojas-Castañeda, Iván Uriel Bahena-Ocampo, Elena Aréchaga-Ocampo, José Díaz-Chávez and Daniel Adrian Landero-Huerta

Int. J. Mol. Sci. 2022, 23(18), 10526; https://doi.org/10.3390/ijms231810526 - 10 Sep 2022

Cited by 2 | Viewed by 2056

Abstract

Some pediatric patients with cryptorchidism preserve cells with gonocyte characteristics beyond their differentiation period, which could support the theory of the gonocyte as a target for malignancy in the development of testicular neoplasia. One of the key molecules in gonocyte malignancy is represented [...] Read more.

Some pediatric patients with cryptorchidism preserve cells with gonocyte characteristics beyond their differentiation period, which could support the theory of the gonocyte as a target for malignancy in the development of testicular neoplasia. One of the key molecules in gonocyte malignancy is represented by microRNAs (miRNAs). The goal of this review is to give an overview of miRNAs, a class of small non-coding RNAs that participate in the regulation of gene expression. We also aim to review the crucial role of several miRNAs that have been further described in the regulation of gonocyte differentiation to spermatogonia, which, when transformed, could give rise to germ cell neoplasia in situ, a precursor lesion to testicular germ cell tumors. Finally, the potential use of miRNAs as diagnostic and prognostic biomarkers in testicular neoplasia is addressed, due to their specificity and sensitivity compared to conventional markers, as well as their applications in therapeutics. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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18 pages, 1142 KiB

Open AccessReview

DNA Methyltransferases: From Evolution to Clinical Applications

by Victor M. Del Castillo Falconi, Karla Torres-Arciga, Genaro Matus-Ortega, José Díaz-Chávez and Luis A. Herrera

Int. J. Mol. Sci. 2022, 23(16), 8994; https://doi.org/10.3390/ijms23168994 - 12 Aug 2022

Cited by 23 | Viewed by 3622

Abstract

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to [...] Read more.

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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Open AccessReview

Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico

by J. Omar Muñoz-Bello, Adela Carrillo-García and Marcela Lizano

Int. J. Mol. Sci. 2022, 23(15), 8566; https://doi.org/10.3390/ijms23158566 - 2 Aug 2022

Cited by 15 | Viewed by 5135

Abstract

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including [...] Read more.

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1–10%, while sublineages differ by 0.5–1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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20 pages, 2903 KiB

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The Kv10.1 Channel: A Promising Target in Cancer

by Enoch Luis, Arely Anaya-Hernández, Paulina León-Sánchez and María Luisa Durán-Pastén

Int. J. Mol. Sci. 2022, 23(15), 8458; https://doi.org/10.3390/ijms23158458 - 30 Jul 2022

Cited by 11 | Viewed by 4105

Abstract

Carcinogenesis is a multistage process involving the dysregulation of multiple genes, proteins, and pathways that make any normal cell acquire a cancer cell phenotype. Therefore, it is no surprise that numerous ion channels could be involved in this process. Since their discovery and [...] Read more.

Carcinogenesis is a multistage process involving the dysregulation of multiple genes, proteins, and pathways that make any normal cell acquire a cancer cell phenotype. Therefore, it is no surprise that numerous ion channels could be involved in this process. Since their discovery and subsequent cloning, ion channels have been established as therapeutic targets in excitable cell pathologies (e.g., cardiac arrhythmias or epilepsy); however, their involvement in non-excitable cell pathologies is relatively recent. Among all ion channels, the voltage-gated potassium channels Kv10.1 have been established as a promising target in cancer treatment due to their high expression in tumoral tissues compared to low levels in healthy tissues. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico)

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