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EGF inhibits constitutive internalization and palmitoylation-dependent degradation of membrane-spanning procancer

M N Adams1, B S Harrington1, Y He1

  • 1Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.

Oncogene
|April 1, 2014
PubMed

Insights

Epidermal growth factor receptor (EGFR) activation stabilizes the cancer-promoting protein CDCP1 by inhibiting its degradation. This EGFR-mediated stabilization and recycling of CDCP1 to the cell surface may drive cancer progression and treatment resistance.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Biology

Background:

  • Many cancers rely on overactive epidermal growth factor receptor (EGFR) signaling.
  • EGFR inhibitors improve survival but benefits are often temporary.
  • CDCP1 (CUB domain-containing protein 1) is a membrane protein implicated in cancer promotion.

Purpose of the Study:

  • To elucidate the novel mechanism linking EGFR and CDCP1.
  • To investigate how EGFR activation affects CDCP1 stability and localization.
  • To understand CDCP1's role in cancer progression and EGFR therapy resistance.

Main Methods:

  • Investigated CDCP1 internalization, palmitoylation, and degradation pathways.
  • Utilized in vivo models and analysis of high-grade serous ovarian tumors.
  • Examined the effect of epidermal growth factor (EGF) stimulation on CDCP1 dynamics.
  • Assessed the impact of CDCP1 relocalization on cell migration.

Main Results:

  • Under normal conditions, cell surface CDCP1 undergoes degradation dependent on palmitoylation.
  • CDCP1 is elevated and palmitoylated in high-grade serous ovarian tumors.
  • EGFR activation by EGF inhibits CDCP1 degradation, promoting its cell surface recycling.
  • Disruption of CDCP1 palmitoylation or EGF treatment enhances cell migration.

Conclusions:

  • EGFR signaling can prolong protein lifespan and promote cell surface recycling of CDCP1.
  • This mechanism offers insights into EGFR therapy resistance.
  • Findings may guide the development of novel treatments for EGFR-dependent cancers.

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