RESUMO
Desmocollin 3 (DSC3) is a transmembrane adhesion protein of desmosomes and involved in carcinogenesis in various cancer types. Downregulation of DSC3 has been reported in colorectal cancer (CRC). However, the function of DSC3 in CRC has not yet been elucidated. In this study, we performed cell-based functional analysis after DSC3 overexpression by stable transfection and knockdown by siRNA in CRC cells. It turned out that overexpression of DSC3 reduced cell proliferation, colony forming ability, induced G0/G1 cell cycle arrest and promoted apoptosis. Further pathway analysis showed that overexpression of DSC3 significantly inhibited the activity of AKT pathway and increased the expression of E-cadherin as well as p53 and p21. In contrast, siRNA-mediated knockdown of DSC3 increased cell proliferation and colony formation, activated the AKT pathway and decreased the expression of E-cadherin as well as p53 and p21. Additionally, in primary CRC patient samples, the expression of DSC3 protein was significantly related to the expression of desmocollin 1 (DSC1) and desmocollin 2 (DSC2) as well as E-cadherin (pâ¯<â¯0.001 respectively). Taken together, our data reveal that DSC3 suppresses CRC cell growth through inhibition of AKT pathway and regulation of E-cadherin. DSC3 may serve as a novel therapeutic target for CRC.