β6 integrin induces the expression of metalloproteinase-3 and metalloproteinase-9 in colon cancer cells via ERK-ETS1 pathway

Huijie Gao; Cheng Peng; Benjia Liang; Muhammad Shahbaz; Song Liu; Ben Wang; Qi Sun; Zhengchuan Niu; Weibo Niu; Enyu Liu; Jiayong Wang; Pengfei Lin; Jian Wang; Jun Niu

doi:10.1016/j.canlet.2014.08.017

β6 integrin induces the expression of metalloproteinase-3 and metalloproteinase-9 in colon cancer cells via ERK-ETS1 pathway

Cancer Lett. 2014 Nov 28;354(2):427-37. doi: 10.1016/j.canlet.2014.08.017. Epub 2014 Aug 15.

Authors

Huijie Gao¹, Cheng Peng¹, Benjia Liang¹, Muhammad Shahbaz¹, Song Liu², Ben Wang¹, Qi Sun¹, Zhengchuan Niu¹, Weibo Niu³, Enyu Liu³, Jiayong Wang³, Pengfei Lin³, Jian Wang⁴, Jun Niu⁵

Affiliations

¹ Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan 250012, Shandong, China.
² Department of Thyroid & Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong, China.
³ Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
⁴ Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, China.
⁵ Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China. Electronic address: niujunsdu@outlook.com.

PMID: 25135220
DOI: 10.1016/j.canlet.2014.08.017

Abstract

We previously reported that β6 integrin played an important role in the progression of colon cancer. In this study, we demonstrated that β6 integrin induced the expression of MMP-3/MMP-9 and the invasion of colon cancer cells. Moreover, that function was abolished by the inhibition of ERK/MAPK pathways or knockdown of ETS1, an important transcription factor of MMP genes. Here, we showed that β6 induced phosphorylation of ETS1 via the ERK/MAPK pathways, through which the MMP-3/MMP-9 promoters were stimulated, thereby leading to the up-regulation of MMP-3/MMP-9, and subsequent the invasion of colon cancer cells.

Keywords: Colon cancer; ETS1; β6 integrin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Colonic Neoplasms / enzymology
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism*
Gene Expression
Gene Knockdown Techniques
HT29 Cells
Humans
Integrin beta Chains / biosynthesis
Integrin beta Chains / genetics
Integrin beta Chains / metabolism*
MAP Kinase Signaling System*
Matrix Metalloproteinase 3 / biosynthesis*
Matrix Metalloproteinase 3 / genetics
Matrix Metalloproteinase 9 / biosynthesis*
Matrix Metalloproteinase 9 / genetics
Molecular Sequence Data
Phosphorylation
Proto-Oncogene Protein c-ets-1 / genetics
Proto-Oncogene Protein c-ets-1 / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Up-Regulation

Substances

ETS1 protein, human
Integrin beta Chains
Proto-Oncogene Protein c-ets-1
RNA, Messenger
integrin beta6
MMP3 protein, human
Matrix Metalloproteinase 3
MMP9 protein, human
Matrix Metalloproteinase 9