Cortactin promotes colorectal cancer cell proliferation by activating the EGFR-MAPK pathway

Oncotarget. 2017 Jan 3;8(1):1541-1554. doi: 10.18632/oncotarget.13652.

Abstract

Cortactin (CTTN) is overexpressed in various tumors, including head and neck squamous cell carcinoma and colorectal cancer (CRC), and can serve as a biomarker of cancer metastasis. We observed that CTTN promotes cancer cell proliferation in vitro and increases CRC tumor xenograft growth in vivo. CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR. CoIP experiments indicate CTTN can interact with c-Cbl in CRC cells. These results demonstrate that CTTN promotes the proliferation of CRC cells and suppresses the degradation of EGFR.

Keywords: MAPK; c-Cbl; colorectal cancer; cortactin(CTTN); epidermal growth factor receptor (EGFR).

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Cortactin / metabolism*
  • ErbB Receptors / metabolism*
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • MAP Kinase Signaling System*
  • Male
  • Mice

Substances

  • CTTN protein, human
  • Cortactin
  • EGFR protein, human
  • ErbB Receptors