Activation of the PI3K-AKT signaling pathway by SPARC contributes to the malignant phenotype of cholangiocarcinoma cells

Autor: Shikang, Deng, Li, Zhang, Jiao, Li, Yan, Jin, Junfeng, Wang
Rok vydání: 2022
Předmět:
Zdroj: Tissue and Cell. 76:101756
ISSN: 0040-8166
DOI: 10.1016/j.tice.2022.101756
Popis: Cholangiocarcinoma (CCA) is a primary biliary epithelium malignancy with limited therapies, poor prognosis and high mortality rate. Nowadays, the molecular mechanisms of CCA remain elusive. SPARC has been proposed to be highly expressed in clinical CCA tissues, but few studies has been elucidated its functions in CCA. In the current study, we aimed to investigate the functional role of SPARC in the progression of CCA. In this study, a significantly increased expression of SPARC was observed in CCA tissues and cells. Knockdown of SPARC by RNA interference significantly impeded the proliferation of CCA cells. Moreover, SPARC silencing hampered the migration and invasion of CCA cells by inhibiting EMT. In parallel, overexpression of SPARC in RBE cells had the opposite effects. Mechanically, SPARC promoted proliferation, migration, invasion, and EMT of CCA cells in vitro via activating the PI3K-AKT signaling. Overall, our integrated analysis revealed that SPARC plays a crucial role in CCA progression via the PI3K-AKT signaling pathway, which suggests that targeting SPARC might represent a promising approach for improving CCA patient's clinical outcome.
Databáze: OpenAIRE