The overexpression of scaffolding protein NEDD9 promotes migration and invasion in cervical cancer via tyrosine phosphorylated FAK and SRC

PLoS One. 2013 Sep 18;8(9):e74594. doi: 10.1371/journal.pone.0074594. eCollection 2013.

Abstract

NEDD9, a focal adhesion scaffolding protein, has been recently proposed to regulate invasion and metastasis in some cancer types, but unknown in cervical cancer. The aim of this study was to determine if NEDD9 was involved in the progression and metastasis of cervical cancer. The experimental results showed NEDD9 protein was overexpressed in cervical cancer compared with normal cervical epithelium tissues. Overexpression of NEDD9 was correlated with histological grading, lymph node metastasis, and FIGO stage of cervical cancer. Silencing NEDD9 resulted in tyrosine dephosphorylation of FAK and SRC oncoproteins, and decreased cell migration and invasion in the cervical carcinoma SiHa and HeLa cells. Overexpression of NEDD9 led to tyrosine phosphorylation of FAK and SRC oncoproteins, and increased cell migration and invasion. Moreover, tyrosine phosphorylation of NEDD9 was significantly decreased via suppressing tyrosine phosphorylation of FAK or SRC, suggesting a positive feedback loop of tyrosine phosphorylation between NEDD9 and FAK or SRC. In addition, our data showed that silencing NEDD9 decreased Vimentin expression and increased E-cadherin expression in cervical cancer cells, and vice versa. E-cadherin was subject to regulation of NEDD9, FAK and SRC, but altered neither tyrosine-phosphorylated nor total NEDD9. Our findings suggest that NEDD9 is overexpressed in cervical cancer tissues and cells, and overexpressed NEDD9 promotes migration and invasion in cervical carcinoma cells, probably via a positive feedback loop of tyrosine phosphorylation between NEDD9 and FAK or SRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement*
  • Female
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Silencing
  • Humans
  • Neoplasm Invasiveness
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism*
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology*
  • Vimentin / metabolism
  • Viral Proteins / metabolism
  • src-Family Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • NEDD9 protein, human
  • Phosphoproteins
  • Vimentin
  • Viral Proteins
  • Phosphotyrosine
  • Focal Adhesion Kinase 1
  • src-Family Kinases

Grant support

The present study was supported by the National Natural Science Foundation of China (Nos. 30801227; 81272862), the Zhejiang Provincial Natural Science Foundation of China (Nos. Y2100403; LY12H16020), the National Basic Research Program of China (No. 2009CB521808), the Fundamental Research Funds for the Central Universities of China and the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.