Author/Authors :
Zhi، نويسنده , , Xiaofei and Tao، نويسنده , , Jinqiu and Xie، نويسنده , , Kunling and Zhu، نويسنده , , Yi and Li، نويسنده , , Zheng and Tang، نويسنده , , Jie and Wang، نويسنده , , Weizhi and Xu، نويسنده , , Hao and Zhang، نويسنده , , Jingjing and Xu، نويسنده , , Zekuan، نويسنده ,
Abstract :
The membrane mucin MUC4 is aberrantly expressed in multiple cancers and is of clinical significance to diagnosis and prognosis in pancreatic cancer. However, the role of MUC4 in angiogenesis and the potential association among these malignant capabilities have not been explored. In this study, we investigated the collective signaling mechanisms associated with MUC4-induced growth, metastasis and angiogenesis in pancreatic cancer. Knockdown of MUC4 in two pancreatic cancer cell lines led to downregulation of lysosomal degradation of E-cadherin by Src kinase through downregulation of pFAK and pSrc pathway. The downregulation of lysosomal degradation of E-cadherin in turn induced the formation of E-cadherin/β-catenin complex and membrane translocation of β-catenin, resulting in the downregulation of Wnt/β-catenin signaling pathway. Thus, the Wnt/β-catenin target genes c-Myc, Cyclin D1, CD44 and VEGF were down-regulated and their malignant functions proliferation, metastasis and angiogenesis were reduced. Taken together, MUC4-induced nuclear translocation of β-catenin is a novel mechanism for growth, metastasis and angiogenesis of pancreatic cancer.
