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In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT

Tobias Ocklenburg1, Fabian Neumann1, Alexandra Wolf1

  • 1Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany.

Scientific Reports
|March 31, 2021
PubMed

Insights

Disulfide isomerase ERp57 knockdown severely inhibits colorectal cancer cell growth and enhances radiosensitivity under hypoxia. This suggests ERp57 is a promising therapeutic target in hypoxic solid tumors.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The endoplasmic reticulum protein 57 (ERp57) is a disulfide isomerase found in various cellular compartments.
  • ERp57 plays a role in diverse cellular functions and has a large network of binding partners.
  • ERp57 is a potential cancer therapy target due to its role in tumor cell proliferation.

Purpose of the Study:

  • To investigate the role of ERp57 in colorectal cancer cell growth under hypoxic conditions.
  • To evaluate ERp57 depletion as a potential therapeutic strategy for solid tumors, which often contain hypoxic areas.

Main Methods:

  • Utilized the colorectal cancer cell line HCT116.
  • Performed knockdown of ERp57.
  • Assessed cell growth inhibition and radiosensitivity under hypoxic conditions (1% O2).
  • Analyzed the expression of key proteins including c-Myc, PLK1, PDPK1, and AKT.

Main Results:

  • ERp57 knockdown resulted in severe growth inhibition of HCT116 cells under hypoxia.
  • Downregulation of c-Myc, PLK1, PDPK1 (PDK1), and AKT (PKB) was observed following ERp57 knockdown in hypoxia.
  • Depletion of ERp57 exhibited a radiosensitizing effect under oxygen deprivation.
  • Knockdown or chemical inhibition of PDPK1 did not significantly inhibit proliferation, suggesting it is not an optimal therapeutic target compared to ERp57.

Conclusions:

  • ERp57 plays a critical role in colorectal cancer cell proliferation and survival under hypoxic conditions.
  • ERp57 is a promising therapeutic target for enhancing cancer treatment efficacy, particularly in hypoxic solid tumors.
  • Targeting ERp57 may overcome treatment resistance associated with tumor hypoxia and improve radiosensitivity.

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