SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer

Journal of Experimental & Clinical Cancer Research

Shiwen Luo³  Nonghua Lv²  Tao Liu³  Junyan Zhang³  Jiang Chen²  Quqin Lu¹  Yao Wang³  Chunyan Zeng³ 

[1] Department of Biostatistics & Epidemiology, School of Public Health, Nanchang University, Nanchang 330006, Jiangxi, China;Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China;Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Street, Donghu District, Nanchang 330006, Jiangxi, China

关键词: Gastric cancer;    Apoptosis;    Degradation;    Hedgehog;    Gli2;    SPOP;   

Others  :  1145588
DOI  :  10.1186/s13046-014-0075-8

 received in 2014-04-28, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

Recent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including gastric cancer. Speckle-type POZ protein, SPOP, is an E3 ubiquitin ligase adaptor, and it is found to inhibit oncogenic signaling. However, the molecular mechanisms are largely unknown.

Methods

In this study, we characterized the expression of SPOP in 88 pairs of gastric cancer tissues and adjacent tissues by immunohistochemical staining and Western blotting. The relationship between SPOP expression and clinical pathologic factors was analyzed. Transfected gastric cancer cell lines were used in cell viability, wound healing and colony formation assays. The interaction of SPOP with Gli2 and other related apoptotic proteins was assessed by immunoprecipitation, Western blotting, real-time PCR and dual luciferase reporter assays. Intracellular interaction of SPOP and Gli2 was visualized by immunofluorescent staining in gastric cancer cells.

Results

Immunohistochemical staining of SPOP can be detected in gastric cancer tissues but much less than adjacent gastric tissues (P?

Conclusions

Our findings indicate that SPOP plays critical roles in suppressing gastric tumorigenesis through inhibiting Hh/Gli2 signaling pathway. It may provide an alternative strategy for developing therapeutic agents of gastric cancer in future.

【 授权许可】

   
2014 Zeng et al.; licensee BioMed Central Ltd.

【 图 表 】

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