Upregulation of CPT1A is essential for the tumor-promoting effect of adipocytes in colon cancer

Xiaopeng Xiong, Yang An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient deprivation and reduced tumor organoid formation in 3D culture and the expression of genes associated with cancer stem cells downstream of Wnt/β-catenin. Mechanistically, CPT1A-dependent FAO promoted the acetylation and nuclear translocation of β-catenin. Furthermore, knockdown of CPT1A blocked the tumor-promoting effect of adipocytes in vivo and inhibited xenograft tumor initiation. Taken together, our findings identify CPT1A-depedent FAO as an essential metabolic pathway that enables the interaction between adipocytes and colon cancer cells.

Original languageEnglish
Article number736
JournalCell Death and Disease
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2020

Bibliographical note

Funding Information:
This work was supported by R01CA133429 (T.G.), R01CA208343 (B.M.E. and T.G.) and a pilot grant from P20GM121327 (University of Kentucky Center for Cancer and Metabolism). The studies were conducted with support provided by the Redox Metabolism, Biospecimen Procurement and Translational Pathology, Cancer Research Informatics, Flow Cytometry and Immune Monitoring, and Biostatistics and Bioinformatics Shared Resource Facilities of the University of Kentucky Markey Cancer Center (P30CA177558) at the University of Kentucky.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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