Upregulation of CPT1A Is Essential for the Tumor-Promoting Effect of Adipocytes in Colon Cancer

Authors

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

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.

Document Type

Article

Publication Date

9-10-2020

Notes/Citation Information

Published in Cell Death & Disease, v. 11, issue 9, article no: 736.

© The Author(s) 2020

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41419-020-02936-6

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).

Repository Citation

Xiong, Xiaopeng; Wen, Yang-An; Fairchild, Rachelle; Zaytseva, Yekaterina Y.; Weiss, Heidi L.; Evers, B. Mark; and Gao, Tianyan, "Upregulation of CPT1A Is Essential for the Tumor-Promoting Effect of Adipocytes in Colon Cancer" (2020). Markey Cancer Center Faculty Publications. 153.
https://uknowledge.uky.edu/markey_facpub/153