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Cancer and Neurodegenerative Diseases: What Is the Link?
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Cancer and Neurodegenerative Diseases: What Is the Link?

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 13516

Special Issue Editors

Dr. Angela Ostuni

E-Mail Website
Guest Editor
Department of Sciences, University of Basilicata, 85100 Potenza, Italy
Interests: cell biology; biochemistry; biomarkers; transcriptome; cancer; ABC transporters; metabolism; recombinant proteins
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Faustino Bisaccia

E-Mail Website
Guest Editor
Department of Sciences, University of Basilicata, 85100 Potenza, Italy
Interests: purification of protein carriers; artificial membranes; transport mechanism; amino acid sequence; transmembrane topography of transport proteins; oligomeric structure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Even though the association is not always clear, and the results have often been contradictory, many epidemiological studies have linked cancer and neurodegenerative disorders.

Cancer and neurodegeneration are two biological processes which, despite working in two opposite directions, i.e., uncontrolled cell proliferation and cellular degeneration, share several genes and biological pathways involved in mitochondrial dysfunction, ROS production, oxidative stress, inflammation, metabolic deregulation, DNA damage, and aberrant cell cycle activation. Aging plays an important role in the link between the two disorders.

This Special Issue invites researchers to exploit the crosstalk between the two disorders through an in-depth investigation into the cellular and molecular mechanisms of the overlapping pathways, with particular attention to considering aspects such as mutational analysis, the role of secretome, and the activation of the immune system. Understanding the mechanisms underlying these interactions might lead to designing therapeutic approaches that can guarantee benefits in cancer surveillance as well as neuroprotection.

Dr. Angela Ostuni
Prof. Dr. Faustino Bisaccia
Guest Editors

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Keywords

  • cancer
  • neurodegenerative diseases
  • polymorphisms
  • miRNAs signature
  • mitochondria
  • aging
  • secretome
  • cytoskeleton
  • antitumor immunity

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Published Papers (4 papers)

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Research

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13 pages, 1398 KiB  
Article
The Crosstalk between HepG2 and HMC-III Cells: In Vitro Modulation of Gene Expression with Conditioned Media
by Prashant Koshal, Ilenia Matera, Vittorio Abruzzese, Angela Ostuni and Faustino Bisaccia
Int. J. Mol. Sci. 2022, 23(22), 14443; https://doi.org/10.3390/ijms232214443 - 21 Nov 2022
Cited by 2 | Viewed by 2027
Abstract
Epidemiological studies have postulated an inverse correlation between developing cancer and neurodegeneration. It is known that the secretome plays a vital role in cell–cell communication in health and disease; the microglia is the resident macrophage of the central nervous system which maintains neuronal [...] Read more.
Epidemiological studies have postulated an inverse correlation between developing cancer and neurodegeneration. It is known that the secretome plays a vital role in cell–cell communication in health and disease; the microglia is the resident macrophage of the central nervous system which maintains neuronal integrity by adapting as the microenvironment changes. The present study aimed to identify, in a cell model, biomarkers that link neurodegenerative diseases to cancer or vice versa. Real-time PCR and western blot analysis were used to characterize the effects on gene and protein expression of human hepatoblastoma (HepG2) and human microglia (HMC-III) cells after exchanging part of their conditioned medium. Biomarkers of the endoplasmic reticulum, and mitophagy and inflammatory processes were evaluated. In both cell types, we observed the activation of cytoprotective mechanisms against any potential pro-oxidant or pro-inflammatory signals present in secretomes. In contrast, HepG2 but not HMC-III cells seem to trigger autophagic processes following treatment with conditioned medium of microglia, thus suggesting a cell-specific adaptive response. Full article
(This article belongs to the Special Issue Cancer and Neurodegenerative Diseases: What Is the Link?)
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17 pages, 2357 KiB  
Article
Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups
by Steven Chang, Lata Singh, Kunal Thaker, Sina Abedi, Mithalesh K. Singh, Tej H. Patel, Marilyn Chwa, Shari R. Atilano, Nitin Udar, Daniela Bota and Maria Cristina Kenney
Int. J. Mol. Sci. 2022, 23(12), 6687; https://doi.org/10.3390/ijms23126687 - 15 Jun 2022
Cited by 3 | Viewed by 2441
Abstract
The aim of this study was to determine the role of retrograde signaling (mitochondria to nucleus) in MCF7 breast cancer cells. Therefore, in the present study, MCF7-H and MCF7-J cybrids were produced using the mitochondria from the same H and J individuals that [...] Read more.
The aim of this study was to determine the role of retrograde signaling (mitochondria to nucleus) in MCF7 breast cancer cells. Therefore, in the present study, MCF7-H and MCF7-J cybrids were produced using the mitochondria from the same H and J individuals that were already used in our non-diseased retinal pigment epithelium (ARPE19) cybrids. MCF7 cybrids were treated with cisplatin and analyzed for cell viability, mitochondrial membrane potential, ROS, and expression levels of genes associated with the cGAS-STING and cancer-related pathways. Results showed that unlike the ARPE19-H and ARPE19-J cybrids, the untreated MCF7-H and MCF7-J cybrids had similar levels of ATP, lactate, and OCR: ECAR ratios. After cisplatin treatment, MCF7-H and MCF7-J cybrids showed similar (a) decreases in cell viability and ROS levels; (b) upregulation of ABCC1, BRCA1 and CDKN1A/P21; and (c) downregulation of EGFR. Cisplatin-treated ARPE19-H and ARPE19-J cybrids showed increased expression of six cGAS-STING pathway genes, while two were increased for MCF7-J cybrids. In summary, the ARPE19-H and ARPE19-J cybrids behave differentially from each other with or without cisplatin. In contrast, the MCF7-H and MCF7-J cybrids had identical metabolic/bioenergetic profiles and cisplatin responses. Our findings suggest that cancer cell nuclei might have a diminished ability to respond to the modulating signaling of the mtDNA that occurs via the cGAS-STING pathway. Full article
(This article belongs to the Special Issue Cancer and Neurodegenerative Diseases: What Is the Link?)
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Review

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27 pages, 1410 KiB  
Review
Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration
by Daniela Passarella, Silvia Ciampi, Valentina Di Liberto, Mariachiara Zuccarini, Maurizio Ronci, Alessandro Medoro, Emanuele Foderà, Monica Frinchi, Donatella Mignogna, Claudio Russo and Carola Porcile
Int. J. Mol. Sci. 2022, 23(16), 8921; https://doi.org/10.3390/ijms23168921 - 10 Aug 2022
Cited by 15 | Viewed by 4847
Abstract
The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the [...] Read more.
The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the receptors in the family, recent studies place low-density lipoprotein receptor-related protein 8 (LRP8) at the center of both neurodegenerative and cancer-related pathways. From one side, its overexpression has been highlighted in many types of cancer including breast, gastric, prostate, lung and melanoma; from the other side, LRP8 has a potential role in neurodegeneration as apolipoprotein E (ApoE) and reelin receptor, which are, respectively, the major risk factor for developing Alzheimer’s disease (AD) and the main driver of neuronal migration, and as a γ-secretase substrate, the main enzyme responsible for amyloid formation in AD. The present review analyzes the contributions of LDL receptors, specifically of LRP8, in both cancer and neurodegeneration, pointing out that depending on various interactions and peculiar processing, the receptor can contribute to both proliferative and neurodegenerative processes. Full article
(This article belongs to the Special Issue Cancer and Neurodegenerative Diseases: What Is the Link?)
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36 pages, 1892 KiB  
Review
Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis
by Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Stephan J Reshkin and Jesús Devesa
Int. J. Mol. Sci. 2022, 23(5), 2454; https://doi.org/10.3390/ijms23052454 - 23 Feb 2022
Cited by 3 | Viewed by 3145
Abstract
The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid–base conceptual frame. At all [...] Read more.
The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid–base conceptual frame. At all levels of study (molecular, biochemical, metabolic, and clinical), the intimate nature of both processes appears to consist of opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranging original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows us to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) is an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Furthermore, within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth. Finally, and for the first time, a new and integrated model of treatment for MS can now be advanced. Full article
(This article belongs to the Special Issue Cancer and Neurodegenerative Diseases: What Is the Link?)
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