Tumor suppressing pathways of LKB1 (IMAGE)
Caption
Tumor suppressing pathways of LKB1. The LKB1-AMPK-mTOR pathway suppresses tumor development. LKB1-AMPK disrupt mTOR activity leading to decreased survival and proliferation while increasing autophagy. Pharmacological compounds that activate the LKB1-AMPK axis and are proven to suppress tumorigenesis include a tankyrase antagonist, metformin, and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Tankyrase antagonists enhance LKB1-STRAD-MO25 complex forming by blocking tankyrase-dependent ubiquitination (U) of LKB1. Metformin increases S428 LKB1 phosphorylation and AMP levels both promoting AMPK activation. AICAR also functions as an AMP mimetic to increase AMPK activity.
Credit
Charles B. Trelford and Trevor G. Shepherd
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License
CC BY-NC-ND