Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention
Abstract
Altered lipid metabolism is a well-recognized feature of solid cancers, including colorectal cancer. In colorectal cancer, upregulation of lipid metabolism contributes to initiation, progression, and metastasis; thus, aberrant lipid metabolism contributes to a poor patient outcome. The inactivating mutation of APC, a vital tumor suppressor in the Wnt signaling pathway, is a key event that occurs early in the majority of colorectal cancer cases. The potential crosstalk between lipid metabolism and APC-driven colorectal cancer is poorly understood. This review collectively highlights and summarizes the limited understanding between mutations in APC and the upregulation of Wnt/beta- catenin signaling and lipid metabolism. The interconnection between APC inactivation and aberrant lipid metabolism activates Wnt/beta-catenin signaling which causes transcriptome, epigenetic, and microbiome changes to promote colorectal cancer initiation and progression. Furthermore, the downstream effects of this collaborative effort between aberrant Wnt/beta-catenin signaling and lipid metabolism are enhanced stemness, cellular proliferation, prooncogenic signaling, and survival. Understanding the mechanistic link between APC inactivation and alterations in lipid metabolism may foster identification of new therapeutic targets to enable development of more efficacious strategies for prevention and/or treatment of colorectal cancer.
Document Type
Article
Publication Date
3-25-2024
Digital Object Identifier (DOI)
https://doi.org/10.3389/fonc.2024.1343061
Funding Information
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by National Cancer Institute training grant T32 CA165990 (COK) and R01 CA249734 (YYZ), and National Institute of Environmental Health Sciences grant P42 ES007380 (University of Kentucky Superfund Research Center, Project 1-YYZ).
Repository Citation
Kelson, Courtney O. and Zaytseva, Yekaterina Y., "Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention" (2024). Markey Cancer Center Faculty Publications. 199.
https://uknowledge.uky.edu/markey_facpub/199
Notes/Citation Information
© 2024 Kelson and Zaytseva. This is an open- access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.