title: GABAB R/GSK-3β/NF-κB signaling pathway regulates the proliferation of colorectal cancer cells.
abstract: 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 γ-Aminobutyric acid receptor (GABAB R) signaling significantly inhibited the colorectal cell HT29 proliferation by arresting the cell at G1 phase. Inhibition of GABAB R activated GSK-3β by reducing the phosphorylation level of GSK-3β. Activation of GSK-3β blocked the function of GABAB R signaling on repressing cell proliferation. We further found that GABAB R activation inhibited NF-κB activity. The promotion of cell proliferation caused by downregulation of GABRB R could be blocked by inhibition of NF-κB activation. Overall, activation of GABAB R leaded to inhibition of GSK-3β activation to repress the NF-κB function during colorectal cancer cell proliferation. This study revealed critical function of GABAB R/GSK-3β/NF-κB signaling pathway on regulating proliferation of colorectal cancer cell, which might provide a potential therapeutic target for clinical colorectal cancer treatment.
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.|Anhui Medical University, Hefei, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of gastroenterology, The Affiliated Clinical College ShenZhen Second People Hospital, Shenzhen, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Anhui Medical University, Hefei, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D018080:Receptors, GABA-B; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Cell cycle; GABABR; GSK-3β; NF-κB; colorectal cancer; proliferation