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Lipid Metabolism in Cancer as a Source of Biomarkers and Therapeutical Targets

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 May 2022) | Viewed by 8105

Special Issue Editors


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Guest Editor
Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
Interests: membrane lipidome; imaging mass spectrometry; inflammatory bowel disease; colorectal cancer; lipid fingerprint; lipid biomarkers; lipid pharmacological targets
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E-Mail Website
Guest Editor
Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
Interests: obesity; colon cancer; gut microbiota; adipose tissue; nutrition

Special Issue Information

Dear Colleagues,

Recent advances in lipidomic and metabolomic techniques have placed lipids in a crucial spot in the field of biomedicine.

On the one hand, it is well known that malignant cells reshape their biosynthetic and bioenergetic requirements to be able to cope with the specific demands associated with the formation and maintenance of the cancer process. In addition to providing energy, the enhancement of lipid uptake and the sustained activation of the de novo lipogenesis make cancer cells the membrane building blocks needed to support rapid proliferation, as well as a repertoire of lipid signaling molecules.

On the other hand, the development of imaging mass spectrometry techniques has helped to demonstrate beyond doubt that the cell lipid profile is cell type-dependent. Even more, cell lipidome has turned out to be highly sensitive to pathophysiological alterations, such as differentiation or tumorigenesis.

However, the regulatory mechanisms that finely control the levels and fate of each one of the lipid species detected remain largely unknown, which make it complicated to infer the biological impact of the results. In this context, the combination of “-omic” techniques, particularly using system biology approaches, could provide new hints to understand the complex networks underlying the control of lipid metabolism. Altogether, the study of lipid metabolism offers a unique opportunity to identify new therapeutic targets and novel specific biomarkers for cancer.

This Special Issue aims to highlight the research and strategies currently used to identify lipid biomarkers for cancer diagnosis, prognosis and treatment monitoring. It also welcomes all those studies seeking to elucidate new regulatory pathways of the lipidome and their role in tumorigenesis and cancer progression by combining different “omic” techniques.

Dr. Gwendolyn Barceló-Coblijn
Dr. Alice Chaplin
Guest Editors

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Keywords

  • membrane lipid metabolism
  • lipidomics
  • transcriptomics
  • genomics
  • proteomics
  • system biology
  • imaging mass spectrometry
  • tumorigenesis
  • differentiation
  • stem cells
  • cancer risk factors
  • cancer
  • lipid biomarkers
  • lipid pharmacological targets

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Published Papers (2 papers)

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Research

22 pages, 3870 KiB  
Article
Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype
by Albert Maimó-Barceló, Lucía Martín-Saiz, José A. Fernández, Karim Pérez-Romero, Santiago Garfias-Arjona, Mónica Lara-Almúnia, Javier Piérola-Lopetegui, Joan Bestard-Escalas and Gwendolyn Barceló-Coblijn
Int. J. Mol. Sci. 2022, 23(6), 2949; https://doi.org/10.3390/ijms23062949 - 9 Mar 2022
Cited by 10 | Viewed by 3649
Abstract
Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on [...] Read more.
Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on GBM and healthy brain tissue could reveal new approaches to address chemotherapy side effects. In this context, we have previously demonstrated the membrane lipidome is highly cell type-specific and very sensitive to pathophysiological states. However, little remains known as to how membrane lipids participate in GBM onset and progression. Hence, we employed an ex vivo model to assess the impact of TMZ treatment on healthy and GBM lipidome, which was established through imaging mass spectrometry techniques. This approach revealed that bioactive lipid metabolic hubs (phosphatidylinositol and phosphatidylethanolamine plasmalogen species) were altered in healthy brain tissue treated with TMZ. To better understand these changes, we interrogated RNA expression and DNA methylation datasets of the Cancer Genome Atlas database. The results enabled GBM subtypes and patient survival to be linked with the expression of enzymes accounting for the observed lipidome, thus proving that exploring the lipid changes could reveal promising therapeutic approaches for GBM, and ways to ameliorate TMZ side effects. Full article
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15 pages, 3398 KiB  
Article
Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma
by Fat-Moon Suk, Yuan-Hsi Wang, Wan-Chun Chiu, Chiao-Fan Liu, Chien-Ying Wu, Tzu-Lang Chen and Yi-Jen Liao
Int. J. Mol. Sci. 2021, 22(16), 8567; https://doi.org/10.3390/ijms22168567 - 9 Aug 2021
Cited by 8 | Viewed by 3286
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the world. Sorafenib is the first-line drug for patients with advanced HCC. However, long-term treatment with sorafenib often results in reduced sensitivity of tumor cells to the drug, leading to acquired resistance. [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the world. Sorafenib is the first-line drug for patients with advanced HCC. However, long-term treatment with sorafenib often results in reduced sensitivity of tumor cells to the drug, leading to acquired resistance. Identifying biomarkers which can predict the response to sorafenib treatment may represent a clinical challenge in the personalized treatment era. Niemann-Pick type C2 (NPC2), a secretory glycoprotein, plays an important role in regulating intracellular free cholesterol homeostasis. In HCC patients, downregulation of hepatic NPC2 is correlated with poor clinical pathological features through regulating mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation. This study aimed to investigate the roles of secretory NPC2-mediated free cholesterol levels as biomarkers when undergoing sorafenib treatment and evaluate its impact on acquired sorafenib resistance in HCC cells. Herein, we showed that NPC2 downregulation and free cholesterol accumulation weakened sorafenib’s efficacy through enhancing MAPK/AKT signaling in HCC cells. Meanwhile, NPC2 overexpression slightly enhanced the sorafenib-induced cytotoxic effect. Compared to normal diet feeding, mice fed a high-cholesterol diet had much higher tumor growth rates, whereas treatment with the free cholesterol-lowering agent, hydroxypropyl-β-cyclodextrin, enhanced sorafenib’s tumor-inhibiting ability. In addition, sorafenib treatment induced higher NPC2 secretion, which was mediated by inhibition of the Ras/Raf/MAPK kinase (MEK)/ERK signaling pathway in HCC cells. In both acquired sorafenib-resistant cell and xenograft models, NPC2 and free cholesterol secretion were increased in culture supernatant and serum samples. In conclusion, NPC2-mediated free cholesterol secretion may represent a candidate biomarker for the likelihood of HCC cells developing resistance to sorafenib. Full article
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