GABABR/GSK-3β/NF-κB signaling pathway regulates the proliferation of colorectal cancer cells

Colorectal cancer is one of the leading causes of highly fatal cancer-related deaths in the whole world. Fast growth is critical characteristic of colorectal cancer, the underlying regulatory mechanism of colorectal cell fast proliferation remains largely unknown. Here, we reported that activation of metabotropic gamma-Aminobutyric acid receptor (GABA(B)R) signaling significantly inhibited the colorectal cell HT29 proliferation by arresting the cell at G1 phase. Inhibition of GABA(B)R activated GSK-3 beta by reducing the phosphorylation level of GSK-3 beta. Activation of GSK-3 beta blocked the function of GABA(B)R signaling on repressing cell proliferation. We further found that GABA(B)R activation inhibited NF-kappa B activity. The promotion of cell proliferation caused by downregulation of GABR(B)R could be blocked by inhibition of NF-kappa B activation. Overall, activation of GABA(B)R leaded to inhibition of GSK-3 beta activation to repress the NF-kappa B function during colorectal cancer cell proliferation. This study revealed critical function of GABA(B)R/GSK-3 beta/ NF-kappa B signaling pathway on regulating proliferation of colorectal cancer cell, which might provide a potential therapeutic target for clinical colorectal cancer treatment.