NDLI: GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon

Content Provider	PubMed Central
Author	Thangaraju, Muthusamy Cresci, Gail A. Liu, Kebin Ananth, Sudha Gnanaprakasam, Jaya P. Browning, Darren D. Mellinger, John D. Smith, Sylvia B. Digby, Gregory J. Lambert, Nevin A. Prasad, Puttur D. Ganapathy, Vadivel
Abstract	Short-chain fatty acids, generated in colon by bacterial fermentation of dietary fiber, protect against colorectal cancer and inflammatory bowel disease. Among these bacterial metabolites, butyrate is biologically most relevant. GPR109A is a G-protein-coupled receptor for nicotinate, but recognizes butyrate with low affinity. Millimolar concentrations of butyrate are needed to activate the receptor. Although concentrations of butyrate in colonic lumen are sufficient to activate the receptor maximally, there have been no reports on the expression/function of GPR109A in this tissue. Here we show that GPR109A is expressed in the lumen-facing apical membrane of colonic and intestinal epithelial cells and that the receptor recognizes butyrate as a ligand. The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines. The tumor-associated silencing of GPR109A involves DNA methylation directly or indirectly. Re-expression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate. Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation. The primary changes in this apoptotic process include downregulation of Bcl-2, Bcl-xL, and cyclin D1, and upregulation of death receptor pathway. In addition, GPR109A/butyrate suppresses NF-κB activation in normal and cancer colon cell lines as well as in normal mouse colon. These studies show that GPR109A mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon.
Related Links	http://dx.doi.org/10.1158/0008-5472.CAN-08-4466
Ending Page	2832
Page Count	7
Starting Page	2826
File Format	PDF
ISSN	15387445
e-ISSN	15387445
Journal	Cancer research
Issue Number	7
Volume Number	69
Language	English
Publisher Date	2009-04-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer

Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer

microRNA-214 functions as a tumor suppressor in human colon cancer via the suppression of ADP-ribosylation factor-like protein 2

15-lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in?

The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival

Ovarian Cancer G Protein–Coupled Receptor 1, a New Metastasis Suppressor Gene in Prostate Cancer

Dependence receptor TrkC is a putative colon cancer tumor suppressor

NLRX1 functions as a tumor suppressor in Pan02 pancreatic cancer cells

GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon

Similar Documents

Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer

Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer

microRNA-214 functions as a tumor suppressor in human colon cancer via the suppression of ADP-ribosylation factor-like protein 2

15-lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in?

The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival

Ovarian Cancer G Protein–Coupled Receptor 1, a New Metastasis Suppressor Gene in Prostate Cancer

Dependence receptor TrkC is a putative colon cancer tumor suppressor

NLRX1 functions as a tumor suppressor in Pan02 pancreatic cancer cells

GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon