MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells

Moorthy P Ponnusamy1, Parthasarathy Seshacharyulu, Arokiapriyanka Vaz

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA. sbatra@unmc.edu.

Abstract

Insights

MUC4 overexpression in ovarian cancer enriches cancer stem cells, potentially via HER2. Targeting MUC4 may offer a new therapeutic strategy for ovarian cancer stem cells.

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology

Background:

  • Cancer stem cells drive tumor growth, relapse, and metastasis.
  • MUC4 is an epithelial cell mucin aberrantly expressed in ovarian cancer, linked to aggressiveness.
  • Targeting cancer stem cells requires identifying specific antigens like MUC4.

Purpose of the Study:

  • To analyze the cancer stem cell population in MUC4-overexpressed ovarian cancer cells.
  • To investigate the role of MUC4 in ovarian cancer stem cell enrichment.

Main Methods:

  • Ectopic MUC4 overexpression in SKOV3 ovarian cancer cells.
  • Western blot and confocal analysis for MUC4, HER2, CD133, ALDH1, and Shh.
  • Flow cytometry (FACS) to quantify cancer stem cell populations (CD133-positive, side population).

Main Results:

  • MUC4 overexpression increased HER2 expression in SKOV3 cells.
  • Increased side population (0.1%) and CD133-positive cancer stem cells observed.
  • MUC4-overexpressing cells formed tumor spheres with CD133, MUC4, HER2, ALDH1, and Shh expression.

Conclusions:

  • MUC4 overexpression enriches ovarian cancer stem cells, potentially mediated by HER2.
  • This finding supports MUC4 as a target for ovarian cancer stem cell-directed therapies.

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