Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake
Saeed Al Mahri, Amal Al Ghamdi, Maaged Akiel, Monira Al Aujan, Sameer Mohammad, Mohammad Azhar Aziz
Abstract
BACKGROUND: genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. AIM: To understand the role of short chain FFARs in CRC. METHODS: genes, which was validated using quantitative real time polymerase chain reaction. Assays for glucose uptake and cyclic adenosine monophosphate (cAMP) generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown. For measuring cell proliferation, we employed real time electrical impedance-based assay available from xCELLigence. RESULTS: gene expression. This prompted us to study the FFAR2 in CRC. Since, FFAR3 shares significant structural and functional homology with FFAR2, we knocked down both these receptors in CRC cell line HCT 116. These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1. Since, FFAR2 and FFAR3 signal through G protein subunit (Gαi), knockdown of these receptors was associated with increased cAMP. Inhibition of protein kinase A (PKA) did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway. CONCLUSION: genes. This study paves the way to understand the mechanism of action of short chain FFARs in CRC.