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Special Issue "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: 30 November 2021.

Special Issue Editors

Dr. Gwendolyn Barceló-Coblijn
E-Mail Website
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
Special Issues and Collections in MDPI journals
Dr. Alice Chaplin
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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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

Published Papers (1 paper)

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Research

Article
Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma
Int. J. Mol. Sci. 2021, 22(16), 8567; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168567 - 09 Aug 2021
Viewed by 548
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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