TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways

Yuhui Wang; Nan Wu; Bo Pang; Dandan Tong; Donglin Sun; Haiming Sun; Chunyu Zhang; Wenjing Sun; Xiangning Meng; Jing Bai; Feng Chen; Jingshu Geng; Songbin Fu; Yan Jin

doi:10.18632/oncotarget.18201

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Research Papers:

TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways

Yuhui Wang, Nan Wu, Bo Pang, Dandan Tong, Donglin Sun, Haiming Sun, Chunyu Zhang, Wenjing Sun, Xiangning Meng, Jing Bai, Feng Chen, Jingshu Geng, Songbin Fu and Yan Jin _

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Oncotarget. 2017; 8:47931-47942. https://doi.org/10.18632/oncotarget.18201

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Abstract

Yuhui Wang1,*, Nan Wu1,*, Bo Pang1,*, Dandan Tong2, Donglin Sun1, Haiming Sun1, Chunyu Zhang1, Wenjing Sun1, Xiangning Meng1, Jing Bai1, Feng Chen1, Jingshu Geng3, Songbin Fu1,4 and Yan Jin1,4

1Laboratory of Medical Genetics, Harbin Medical University, Harbin, China

2Department of Pathology, Harbin Medical University, Harbin, China

3Department of Pathology, Third Affiliated Clinical Hospital, Harbin Medical University, Harbin, China

4Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China

*These authors have contributed equally to this work

Correspondence to:

Yan Jin, email: [email protected]

Songbin Fu, email: [email protected], [email protected]

Keywords: TRIB1, colorectal carcinoma, migration, invasion, MMP-2

Received: November 30, 2016 Accepted: May 01, 2017 Published: May 25, 2017

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis (P=0.043) and advanced staging (P=0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.

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Research Papers:

TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways

Abstract