The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer
Open accessAbstract
Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients. Co-culture of adipocytes with colon cancer cells led to a transfer of free fatty acids that released from the adipocytes to the cancer cells. Uptake of fatty acids allowed the cancer cells to survive nutrient deprivation conditions by upregulating mitochondrial fatty acid β-oxidation. Mechanistically, co-culture of adipocytes or treating cells with fatty acids induced autophagy in colon cancer cells as a result of AMPK activation. Inhibition of autophagy attenuated the ability of cancer cells to utilize fatty acids and blocked the growth-promoting effect of adipocytes. In addition, we found that adipocytes stimulated the expression of genes associated with cancer stem cells and downregulated genes associated with intestinal epithelial cell differentiation in primary colon cancer cells and mouse tumor organoids. Importantly, the presence of adipocytes promoted the growth of xenograft tumors in vivo. Taken together, our results show that adipocytes in the tumor microenvironment serve as an energy provider and a metabolic regulator to promote the growth and survival of colon cancer cells.
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Cites
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Cited by
Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
Snaebjornsson, M. T., Janaki-Raman, S., & Schulze, A. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.010 · Cited by 1,097
Lipid metabolism in cancer: New perspectives and emerging mechanisms
Broadfield, L. A., Pane, A. A., Talebi, A., Swinnen, J. V., & Fendt, S.-M. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.013 · Cited by 758
Fatty acid oxidation: An emerging facet of metabolic transformation in cancer
Ma, Y., Temkin, S. M., Hawkridge, A. M., Guo, C., Wang, W., Wang, X.-Y., & Fang, X. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.006 · Cited by 531
Ulgen, E., Ozisik, O., & Sezerman, O. U. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00858 · Cited by 469
Lipids in the tumor microenvironment: From cancer progression to treatment
Corn, K. C., Windham, M. A., & Rafat, M. (2020) · Progress in Lipid Research · doi:10.1016/j.plipres.2020.101055 · Cited by 469
Metadata
- Authors
- Wen, Y.-A., Xing, X., Harris, J. W., Zaytseva, Y. Y., Mitov, M. I., Napier, D. L., Weiss, H. L., Mark Evers, B., & Gao, T.
- Venue
- Cell Death & Disease
- Published
- 2017-02-02
- Volume
- 8
- Issue
- 2
- Pages
- e2593-e2593
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W2583960272
- Cited by
- 291
- References
- 12
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- gold
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- Wen, Y.-A., Xing, X., Harris, J. W., Zaytseva, Y. Y., Mitov, M. I., Napier, D. L., Weiss, H. L., Mark Evers, B., & Gao, T. (2017). Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer. Cell Death & Disease. https://doi.org/10.1038/cddis.2017.21
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