Upregulation of TrkB Promotes Epithelial-Mesenchymal Transition and Anoikis Resistance in Endometrial Carcinoma

被引：68

作者：

Bao, Wei ^{[1
]}

Qiu, Haifeng ^{[2
]}

Yang, Tingting ^{[2
]}

Luo, Xin ^{[3
]}

Zhang, Huijuan ^{[4
]}

Wan, Xiaoping ^{[2
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Obstet & Gynecol, Int Peace Matern & Child Hlth Hosp, Sch Med, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Dept Obstet & Gynecol, Shanghai Peoples Hosp 1, Sch Med, Shanghai 200030, Peoples R China

[3] Shanghai Jiao Tong Univ, Dept Ctr Res Lab, Int Peace Matern & Child Hlth Hosp, Sch Med, Shanghai 200030, Peoples R China

[4] Shanghai Jiao Tong Univ, Dept Pathol, Int Peace Matern & Child Hlth Hosp, Sch Med, Shanghai 200030, Peoples R China

来源：

PLOS ONE | 2013年 / 8卷 / 07期

基金：

中国国家自然科学基金;

关键词：

NEUROTROPHIC RECEPTOR TRKB; PANCREATIC-CANCER CELLS; KINASE-B; NEUROBLASTOMA-CELLS; TUMOR PROGRESSION; FACTOR ACTIVATION; COLON-CANCER; METASTASIS; EXPRESSION; BDNF;

D O I：

10.1371/journal.pone.0070616

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mechanisms governing the metastasis of endometrial carcinoma (EC) are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05) and lymphovascular space involvement (p<0.05) in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT). RNA interference (RNAi)-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC.

引用

页数：17

共 47 条

[1] Tyrosine receptor kinase B (TrkB) protein expression in the human endometrium [J].