Therapeutic Suppression of FAK-AKT Signaling Overcomes Resistance to SHP2 Inhibition in Colorectal Carcinoma.

ABSTRACT: SHP2 mediates signaling from multiple receptor tyrosine kinases (RTKs) to extracellular signal-regulated kinase (ERK) and Ser and Thr kinase AKT, and its inhibitors offer an unprecedented opportunity for cancer treatment. Although the ERK signaling variation after SHP2 inhibition has been well investigated, the AKT signaling variation in colorectal carcinoma (CRC) is still unknown. Therefore, we performed immunohistochemistry and bioinformatics analyses to explore the significance of p-SHP2 in CRC. A panel of CRC cell lines with the SHP2 inhibitor, SHP099, was used to assess the effects on viability and signaling. The inhibitors of AKT and focal adhesion kinase (FAK) signaling were examined in combination with SHP099 as potential strategies to enhance the efficacy and overcome resistance.

SUBMITTER: Li Y 

PROVIDER: S-EPMC8591248 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature