Therapeutic inhibition of SGK1 suppresses colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC. Cancer treatment: Putting the brakes on colorectal cancer A signaling protein that promotes survival and aggressive growth of tumor cells may offer a useful drug target for colorectal cancer. Several studies have tentatively linked serum- and glucocorticoid-inducible kinase 1 (SGK1) with malignant growth. Findings from Shanghai University researchers Bin Xu and Junjie Xiao and colleagues now indicate a prominent role for this protein in colorectal cancer progression. They determined that the SGK1 protein is present at high levels in human tumor specimens, and showed that it can promote proliferation, migration and resistance to drug-induced cell death in cultured cancer cells. These tumorigenic effects could be countered by treatment with a chemical inhibitor of SGK1, both in cultured cells and in mice implanted with colorectal cancer cells. These findings could therefore indicate a new avenue of treatment for this highly lethal disease.