Suppression of the epithelial-mesenchymal transition by SHARP1 is linked to the NOTCH1 signaling pathway in metastasis of endometrial cancer

BMC Cancer

Xiaoping Wan¹  Huihui Wang³  Jingyun Wang²  Meiting Qiu²  Zheng Chen³  Wen Lu¹  Fangyuan Wang³  Qi Che³  Haifeng Qiu³  Xiaoying He²  Yun Liao³ 

[1]Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, No. 536, Changle Road, Shanghai 200080, China

[2]Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

[3]Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

关键词: NOTCH1;    EMT;    SHARP1;    Metastasis;    Endometrial cancer;   

Others  :  1125355
DOI  :  10.1186/1471-2407-14-487

 received in 2014-02-25, accepted in 2014-06-30,  发布年份 2014

【 摘 要 】

Background

Mechanisms governing the metastasis of endometrial cancer (EC) are poorly defined. Recent data support a role for Enhancer-of-split and hairy-related protein 1 (SHARP1), a basic helix-loop-helix transcription repressor, in regulating invasiveness and angiogenesis of several human cancers. However, the role of SHARP1 in metastasis of EC remains unclear.

Methods

Human EC cell lines (Ishikawa and HEC-1B) were used. SHARP1 was upregulated by lentivirus transduction, while intracellular domain of NOTCH1 (ICN) were upregulated by transient transfection with plasmids. Effects of SHARP1 on cell migration and invasion were evaluated by wound healing assay and transwell invasion assay. Experimental metastasis assay were performed in nude mice. Effects of SHAPR1 on protein levels of target genes were detected by western blotting. Furthermore, the association between SHARP1 and the NOTCH1/EMT pathway was further verified in EC tissue specimens by immunohistochemical analysis.

Results

Overexpression of SHARP1 in EC cells inhibited cell migration, invasion, and metastasis. Exogenous SHARP1 overexpression affected the proteins levels of genes involved in EMT process and NOTCH1 signaling pathway. Upregulation of ICN in SHARP1-overexpressing Ishikawa cells induced cell migration and an EMT phenotype. Additionally, immunohistochemical analysis demonstrated that SHARP1 protein levels were lower in metastatic EC than in primary tumors, and statistical analysis revealed correlations between levels of SHARP1 and markers of EMT and NOTCH1 signaling pathway in human EC tissue specimen.

Conclusions

This work supports a role for SHARP1 in suppressing EMT and metastasis in EC by attenuating NOTCH1 signaling. Therefore, SHARP1 may be a novel marker for lymphatic metastasis in EC patients.

【 授权许可】

   
2014 Liao et al.; licensee BioMed Central Ltd.

【 图 表 】

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