E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells

Journal of Translational Medicine

Minhua Zheng²  Zhenggang Zhu¹  Zhihai Mao²  Xuehua Chen¹  Bo Feng²  Yingjun Quan²  Pu Li¹  Ao Huang²  Hongchao Zhao² 

[1] Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Rd, Shanghai 200025, People’s Republic of China;Shanghai Minimally Invasive Surgery Center, Shanghai, China

关键词: EMT;    YAP;    Colorectal cancer;    E2A;    Metastasis;   

Others  :  824036
DOI  :  10.1186/1479-5876-11-317

 received in 2013-09-12, accepted in 2013-11-25,  发布年份 2013

【 摘 要 】

Background

E2A gene, which encodes two basic helix–loop–helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive.

Methods

qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively.

Results

E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency.

Conclusion

Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression.

【 授权许可】

   
2013 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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