The type III TGF-β receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-β signaling

被引：60
作者：
Lee, Jason D. [1 ,2 ]
Hempel, Nadine [1 ]
Lee, Nam Y. [1 ]
Blobe, Gerard C. [1 ,2 ]
机构：
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA
[2] Duke Univ, Med Ctr, Dept Med, Durham, NC 27708 USA
来源：
CARCINOGENESIS | 2010年 / 31卷 / 02期
关键词：
GROWTH-FACTOR-BETA; DOWN-REGULATION; HUMAN-DISEASE; EXPRESSION; BETAGLYCAN; MOTILITY; TUMORIGENESIS; INVASIVENESS; ENDOCYTOSIS; MODULATION;
D O I：
10.1093/carcin/bgp271
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Loss of expression of the type III transforming growth factor-beta receptor (T beta RIII or betaglycan), a transforming growth factor-beta (TGF-beta) superfamily co-receptor, is common in human breast cancers. T beta RIII suppresses cancer progression in vivo by reducing cancer cell migration and invasion by largely unknown mechanisms. Here, we demonstrate that the cytoplasmic domain of T beta RIII is essential for T beta RIII-mediated downregulation of migration and invasion in vitro and T beta RIII-mediated inhibition of breast cancer progression in vivo. Functionally, the cytoplasmic domain of T beta RIII is required to attenuate TGF-beta signaling, whereas T beta RIII-mediated attenuation of TGF-beta signaling is required for T beta RIII-mediated inhibition of migration and invasion. Mechanistically, both T beta RIII-mediated inhibition of TGF-beta signaling and T beta RIII-mediated inhibition of invasion occur through the interaction of the cytoplasmic domain of T beta RIII with the scaffolding protein GAIP-interacting protein C-terminus (GIPC). Taken together, these studies support a functional role for the T beta RIII cytoplasmic domain interacting with GIPC to suppress breast cancer progression.
引用
收藏
页码：175 / 183
页数：9
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