mTOR Complex Component Rictor Interacts with PKCζ and Regulates Cancer Cell Metastasis

作者：Zhang, Fei; Zhang, Xiaofang; Li, Menghui; Chen, Peng; Zhang, Bin; Guo, Hua; Cao, Wenfeng; Wei, Xiying; Cao, Xuchen; Hao, Xishan; Zhang, Ning^*

来源：Cancer Research, 2010, 70(22): 9360-9370.

DOI：10.1158/0008-5472.CAN-10-0207

• KINASE-C ZETA
• AKT PHOSPHORYLATION
• CHEMOKINE RECEPTORS
• MEDIATED ACTIVATION
• INHIBITS MIGRATION
• CHEMOTAXIS
• GROWTH
• MOTILITY
• OVEREXPRESSION
• DICTYOSTELIUM

Epidermal growth factor (EGF) mediates breast cancer cell chemotaxis and metastasis through mechanisms that involve the growth-regulatory mammalian target of rapamycin (mTOR) complex mTORC2, but the mechanisms involved remain obscure. Here, we report that the rapamycin-insensitive mTORC2 component protein Rictor is a critical mediator of metastasis in breast cancer cells. In patients with ductal carcinoma, Rictor expression was associated with increased lymph node metastasis. EGF induced translocation and colocalization of Rictor with protein kinase C zeta (PKC zeta), a pivotal molecule in chemotaxis signaling. Further, Rictor coimmunoprecipitated with PKC zeta in the absence of the mTORC2 complex. Small interfering RNA-mediated knockdown of Rictor inhibited EGF-induced PKC zeta phosphorylation and translocation along with phosphorylation of the key F-actin binding protein cofilin. In parallel, Rictor knockdown reduced cellular chemotactic capacity and ablated pulmonary metastasis in a xenograft mouse model of breast cancer. Our findings identify Rictor as an important mediator of chemotaxis and metastasis in breast cancer cells. Cancer Res; 70(22); 9360-70.

• 出版日期2010-11-15
• 单位天津医科大学