KRAS mutation-independent downregulation of MAPK/PI3K signaling in colorectal cancer.

ABSTRACT: KRAS is a gatekeeper gene in human colorectal tumorigenesis. KRAS is 'undruggable'; hence, efforts have been diverted to inhibit downstream RAF/MEK/ERK and PI3K/Akt signaling. Nevertheless, none of these inhibitors has progressed to clinical use despite extensive trials. We examined levels of phospho-ERK1/2(T202/Y204) and phospho-Akt1/2/3(S473) in human colorectal tumor compared to matched mucosa with semi-quantitative near-infrared western blot and confocal fluorescence immunohistochemistry imaging. Surprisingly, 75.5% (25/33) of tumors had lower or equivalent phospho-ERK1/2 and 96.9% (31/32) of tumors had lower phospho-Akt1/2/3 compared to matched mucosa, irrespective of KRAS mutation status. In contrast, we discovered KRAS-dependent SOX9 upregulation in 28 of the 31 (90.3%) tumors. Thes

SUBMITTER: Lam KK 

PROVIDER: S-EPMC8895447 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature