Open AccessGABA B R / GSK ‐3 β / NF ‐ κ B signaling pathway regulates the proliferation of colorectal cancer cells
Author(s) -
Shu Qing,
Liu Jun,
Liu Xiupeng,
Zhao Sufang,
Li Hualin,
Tan Yonggang,
Xu Jianming
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.686
Subject(s) - nf κb , signal transduction , cell growth , phosphorylation , microbiology and biotechnology , chemistry , biology , biochemistry
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 ( GABA B R ) signaling significantly inhibited the colorectal cell HT 29 proliferation by arresting the cell at G1 phase. Inhibition of GABA B R activated GSK ‐3 β by reducing the phosphorylation level of GSK ‐3 β . Activation of GSK ‐3 β blocked the function of GABA B R signaling on repressing cell proliferation. We further found that GABA B R activation inhibited NF ‐ κ B activity. The promotion of cell proliferation caused by downregulation of GABR B R could be blocked by inhibition of NF ‐ κ B activation. Overall, activation of GABA B R leaded to inhibition of GSK ‐3 β activation to repress the NF ‐ κ B function during colorectal cancer cell proliferation. This study revealed critical function of GABA B R / GSK ‐3 β / NF ‐ κ B signaling pathway on regulating proliferation of colorectal cancer cell, which might provide a potential therapeutic target for clinical colorectal cancer treatment.