WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C

Ya-ling Tang; Xin Liu; Shi-yu Gao; Hao Feng; Ya-ping Jiang; Sha-sha Wang; Jing Yang; Jian Jiang; Xiang-rui Ma; Ya-jie Tang; Yu Chen; Xin-hua Liang

doi:10.18632/oncotarget.3320

WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C

Oncotarget. 2015 Apr 20;6(11):9031-44. doi: 10.18632/oncotarget.3320.

Authors

Ya-ling Tang^{1

2}, Xin Liu², Shi-yu Gao², Hao Feng², Ya-ping Jiang², Sha-sha Wang², Jing Yang², Jian Jiang², Xiang-rui Ma², Ya-jie Tang³, Yu Chen¹, Xin-hua Liang^{2

4}

Affiliations

¹ Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
² State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
³ Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People's Republic of China.
⁴ Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.

Abstract

The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

Keywords: adenoid cystic carcinoma (ACC); invasion; metastasis; salivary gland; wild-type p53 induced phosphatase 1 (WIP1).

Publication types

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

MeSH terms

Animals
Carcinoma, Adenoid Cystic / metabolism
Carcinoma, Adenoid Cystic / mortality
Carcinoma, Adenoid Cystic / pathology*
Cell Line, Tumor
Cell Movement
DNA, Complementary / genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic*
Heterografts
Humans
Kaplan-Meier Estimate
Matrix Metalloproteinase 9 / biosynthesis*
Matrix Metalloproteinase 9 / genetics
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / physiology*
Prognosis
Proportional Hazards Models
Protein Phosphatase 2C
RNA Interference
RNA, Small Interfering / genetics
Random Allocation
Recombinant Fusion Proteins / metabolism
Salivary Gland Neoplasms / metabolism
Salivary Gland Neoplasms / mortality
Salivary Gland Neoplasms / pathology*
Signal Transduction
Transduction, Genetic
Transfection
Vascular Endothelial Growth Factor C / biosynthesis*
Vascular Endothelial Growth Factor C / genetics

Substances

DNA, Complementary
Neoplasm Proteins
RNA, Small Interfering
Recombinant Fusion Proteins
VEGFC protein, human
Vascular Endothelial Growth Factor C
PPM1D protein, human
Phosphoprotein Phosphatases
Ppm1d protein, mouse
Protein Phosphatase 2C
MMP9 protein, human
Matrix Metalloproteinase 9