GOLM1 Modulates EGFR/RTK Cell-Surface Recycling to Drive Hepatocellular Carcinoma Metastasis

Cancer Cell. 2016 Sep 12;30(3):444-458. doi: 10.1016/j.ccell.2016.07.017. Epub 2016 Aug 25.

Abstract

The mechanism of cancer metastasis remains poorly understood. Using gene profiling of hepatocellular carcinoma (HCC) tissues, we have identified GOLM1 as a leading gene relating to HCC metastasis. GOLM1 expression is correlated with early recurrence, metastasis, and poor survival of HCC patients. Both gain- and loss-of-function studies determine that GOLM1 acts as a key oncogene by promoting HCC growth and metastasis. It selectively interacts with epidermal growth factor receptor (EGFR) and serves as a specific cargo adaptor to assist EGFR/RTK anchoring on the trans-Golgi network (TGN) and recycling back to the plasma membrane, leading to prolonged activation of the downstream kinases. These findings reveal the functional role of GOLM1, a Golgi-related protein, in EGFR/RTK recycling and metastatic progression of HCC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Transfection
  • Up-Regulation
  • Young Adult

Substances

  • GOLM1 protein, human
  • Membrane Proteins
  • EGFR protein, human
  • ErbB Receptors