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Insight into Fatty Acid Metabolism in Colorectal Cancer

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Special Issue Information
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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 11952

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Special Issue Editor

Dr. Yekaterina Zaytseva

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Guest Editor

Toxicology and Cancer Biology, University of Kentucky College of Medicine, USA
Interests: colorectal cancer; metastasis; lipid metabolism; fatty acid synthase (FASN) and de novo lipid synthesis; FASN-targeted therapies and CRC resistance; exogeneous fatty acid uptake; colorectal cancer and obesity

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Despite advances in our understanding of the molecular basis of CRC and the increasing number of targeted therapies, treatment of CRC frequently remains disappointing.

Altered lipid metabolism, a common feature of cancer cells, is rapidly emerging as a potential target for therapeutic intervention in CRC. Fatty acids, which can be obtained from diet or synthesized de novo from carbohydrate precursors, are important substrates for energy metabolism and essential components of cell membranes. Lipids are also implicated in signal transduction; intracellular trafficking; posttranslational modifications; and cell secretion, migration, and invasion.

Activation of lipogenesis and overexpression of lipogenic enzymes such as fatty acid synthase (FASN) correlate with a poorer prognosis and shorter disease-free survival in CRC. While most tumors are dependent on fatty acid synthesis, they can also scavenge lipids from their environment. Epidemiological studies demonstrate that a high-fat diet and obesity increase the risk of CRC 1.5–2.0-fold. Furthermore, recent data show that rates of CRC are increasing in younger populations and obesity is being one of the major factors that contribute to the raising rate of this disease. These new alarming data support the urgent need to better understand the mechanisms behind how lipid metabolism contributes to the initiation and progression of CRC.

Lipid metabolism has been actively explored as a therapeutic target, and several clinical trials are underway. Even though early data from clinical trials show promising results, there are multiple unanswered questions about lipid-driven metabolic alterations that promote CRC and about how diet and obesity contribute to lipid-metabolism-targeted therapy responses. The Special Issue “Insight into Fatty Acid Metabolism in Colorectal Cancer” will bring together experts in the field of lipid metabolism in CRC to share novel research, expand our knowledge, and stimulate discussions on this topic.

Dr. Yekaterina Zaytseva
Guest Editor

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 submissions that pass pre-check are 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

colorectal cancer
colorectal cancer metastasis
de novo lipid synthesis
fatty acid transporters and fatty acid uptake in CRC
obesity and CRC
lipid metabolism-targeted therapies

Published Papers (3 papers)

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Editorial

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5 pages, 229 KiB

Open AccessEditorial

Lipid Metabolism as a Targetable Metabolic Vulnerability in Colorectal Cancer

by Yekaterina Zaytseva

Cancers 2021, 13(2), 301; https://doi.org/10.3390/cancers13020301 - 15 Jan 2021

Cited by 26 | Viewed by 2429

Abstract

Colorectal cancer (CRC), the second leading cause of cancer-related deaths according to the World Health Organization, remains a substantial public health problem worldwide [...] Full article

(This article belongs to the Special Issue Insight into Fatty Acid Metabolism in Colorectal Cancer)

Research

Jump to: Editorial

20 pages, 2429 KiB

Open AccessArticle

Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells

by Martina Karasová, Jiřina Procházková, Zuzana Tylichová, Radek Fedr, Miroslav Ciganek, Miroslav Machala, Zdeněk Dvořák, Barbora Vyhlídalová, Iveta Zůvalová, Jiří Ehrmann, Jan Bouchal, Zdeněk Andrysík and Jan Vondráček

Cancers 2022, 14(17), 4245; https://doi.org/10.3390/cancers14174245 - 31 Aug 2022

Cited by 6 | Viewed by 3097

Abstract

The aryl hydrocarbon receptor (AhR) plays a wide range of physiological roles in cellular processes such as proliferation, migration or control of immune responses. Several studies have also indicated that AhR might contribute to the regulation of energy balance or cellular metabolism. We observed that the AhR is upregulated in tumor epithelial cells derived from colon cancer patients. Using wild-type and the corresponding AhR knockout (AhR KO) variants of human colon cancer cell lines HCT116 and HT-29, we analyzed possible role(s) of the AhR in cell proliferation and metabolism, with a focus on regulation of the synthesis of fatty acids (FAs). We observed a decreased proliferation rate in the AhR KO cells, which was accompanied with altered cell cycle progression, as well as a decreased ATP production. We also found reduced mRNA levels of key enzymes of the FA biosynthetic pathway in AhR KO colon cancer cells, in particular of stearoyl-CoA desaturase 1 (SCD1). The loss of AhR was also associated with reduced expression and/or activity of components of the PI3K/Akt pathway, which controls lipid metabolism, and other lipogenic transcriptional regulators, such as sterol regulatory element binding transcription factor 1 (SREBP1). Together, our data indicate that disruption of AhR activity in colon tumor cells may, likely in a cell-specific manner, limit their proliferation, which could be linked with a suppressive effect on their endogenous FA metabolism. More attention should be paid to potential mechanistic links between overexpressed AhR and colon tumor cell metabolism. Full article

(This article belongs to the Special Issue Insight into Fatty Acid Metabolism in Colorectal Cancer)

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17 pages, 4020 KiB

Open AccessEditor’s ChoiceArticle

Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression

by James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers and Yekaterina Y. Zaytseva

Cancers 2022, 14(1), 252; https://doi.org/10.3390/cancers14010252 - 5 Jan 2022

Cited by 26 | Viewed by 5177

Abstract

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation of MMP28, a novel member of the metallopeptidase family of proteins. Using shRNA-mediated knockdown and overexpression of CD36, we confirmed that CD36 regulates MMP28 expression in CRC cells. siRNA-mediated knockdown of MMP28 decreases invasion of CRC cells, suggesting that MMP28 regulates the metastatic properties of cells downstream of CD36. Importantly, high expression of MMP28 leads to a significant decrease in active E-cadherin and an increase in the products of E-cadherin cleavage, CTF1 and CTF2. In summary, upregulation of CD36 expression promotes the metastatic properties of CRC via upregulation of MMP28 and an increase in E-cadherin cleavage, suggesting that targeting the CD36–MMP28 axis may be an effective therapeutic strategy for CRC metastasis. Full article

(This article belongs to the Special Issue Insight into Fatty Acid Metabolism in Colorectal Cancer)

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