Caveolin-1 silencing arrests the proliferation of metastatic lung cancer cells through the inhibition of STAT3 signaling

Cell Signal. 2012 Jul;24(7):1390-7. doi: 10.1016/j.cellsig.2012.02.015. Epub 2012 Mar 3.

Abstract

Cav-1 is an essential structural constituent of caveolae implicated in mitogenic signaling, oncogenesis, angiogenesis, neurodegenerative diseases and senescence. Its role as a tumor suppressor gene or as a tumor promoter seems to strictly depend on cell type and tumor stage/grade. The high expression of Cav-1 in some tumors in vivo, amongst which lung adenocarcinoma, is associated with increased tumor aggressiveness, metastatic potential and suppression of apoptosis. In the present study we investigated the role of Cav-1 in metastatic lung cancer proliferation. Cell lines were from metastatic lesions of lung adenocarcinoma (RAL) and of small cell lung carcinoma (SCLC-R1), in which we found Cav-1 expressed at high levels. Results show that siRNA-mediated down-regulation of Cav-1 caused stable arrest of proliferation in both cell lines. A marked reduction of cyclin D1 and of CDK4 expression was evident in the cells transfected with Cav-1 siRNA and consequently of phospho-Rb on ser(795) and ser(780). Furthermore, a significant decrease of the expression of phosphorylated AKT and of its down-stream effectors phosphorylated ERK and STAT3 was evident. Together, these findings indicate that Cav-1 silencing induces an arrest of human metastatic lung proliferation in vitro by a new inhibitory pathway in lung cancer and provide new insights into the molecular mechanisms underlying the pro-survival and tumor-promoting functions of Cav-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma of Lung
  • Caveolin 1 / genetics*
  • Caveolin 1 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Neoplasm Metastasis
  • Oncogene Protein v-akt / metabolism
  • RNA, Small Interfering
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction
  • Small Cell Lung Carcinoma / genetics*

Substances

  • CAV1 protein, human
  • Caveolin 1
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Oncogene Protein v-akt
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4