Osteopontin Knockdown Inhibits αv,β3 Integrin-Induced Cell Migration and Invasion and Promotes Apoptosis of Breast Cancer Cells by Inducing Autophagy and Inactivating the PI3K/Akt/mTOR Pathway

Cellular Physiology and Biochemistry

关键词: Osteopontin;    Integrin αv;    β3;    Cell migration;    Cell invasion;    Apoptosis;    RNA interference;    Phosphoinositide 3-kinase;    Akt;    mTOR;   

DOI  :  10.1159/000358670

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Osteopontin (OPN) is associated with tumor formation, progression and metastasis, and increased OPN levels have been associated with poor survival in breast cancer. We investigated the mechanisms responsible for OPN activity, and the relationships between OPN expression and clinical parameters in breast cancer. Methods OPN mRNA and protein levels were compared in malignant and benign breast tumors by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and levels in breast cancer cells were determined by PCR and western blotting. The effects of lentiviral-mediated knockdown of OPN on OPN and α_v,β₃ integrin expression, cell invasion and migration, autophagy and apoptosis were analyzed in MDA-MB-231 cells. Results OPN expression increased with aggressiveness of breast cancer phenotype. OPN knockdown inhibited α_v,β₃ integrin expression in MDA-MB-231 cells, with subsequent inhibition of cell migration and invasion. Knockdown also inhibited the PI3K/Akt/mTOR pathway, promoted expression of the autophagy-related gene products LC3 and Beclin 1, and increased apoptosis. OPN expression was positively associated with tumor grade and lymph node metastasis. Conclusion These results suggest that knockdown of OPN may inhibit breast cancer metastasis by regulating α_v,β₃ integrin expression and inducing autophagy and subsequent inhibition of PI3K/Akt/mTOR signaling, thus providing further insights into the complex mechanisms regulating tumor growth and metastasis.

【 授权许可】

CC BY-NC-ND