The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
G‐protein‐coupled receptor for short‐chain fatty acids suppresses colon cancer
Abstract
GPR43 is a G‐protein‐coupled receptor for short‐chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues ( N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues ( N = 70) and their corresponding lymph node metastatic adenocarcinomas ( N = 38). RT‐PCR analysis detected the presence of full length GPR43 mRNA in only one (HT‐29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin‐dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA‐induced cell proliferation inhibition and apoptotic cell death in colon cancer.
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Cites
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“It may also enhance assembly and activity in complexes of CDK4 or CDK6 and cyclin D.(39) The carboxy-terminal region of p21 is sufficient to bind and inhibit PCNA, a subunit of DNA polymerase, and may coordinate DNA replication with cell cycle progression.”
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“Propionate was also shown to inhibit cell growth and trigger apoptosis in other colorectal carcinoma cells.(15,16) The data suggest that SCFAs guard against colon carcinogenesis.”
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Cited by
From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites
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The role of short chain fatty acids in health and disease
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Garrett, W. S. (2015) · Science · doi:10.1126/science.aaa4972 · Cited by 1,404
Metadata
- Authors
- Tang, Y., Chen, Y., Jiang, H., Robbins, G. T., & Nie, D.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2010-10-26
- Volume
- 128
- Issue
- 4
- Pages
- 847-856
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2023113611
- Cited by
- 281
- References
- 7
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- closed
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- Tang, Y., Chen, Y., Jiang, H., Robbins, G. T., & Nie, D. (2011). G‐protein‐coupled receptor for short‐chain fatty acids suppresses colon cancer. International Journal of Cancer. https://doi.org/10.1002/ijc.25638
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