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GATA3 as a master regulator and therapeutic target in ovarian high-grade serous carcinoma stem cells

Hsiang-Ju Chen1,2,3, Rui-Lan Huang4,5,6, Phui-Ly Liew7,8

  • 1Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.

International Journal of Cancer
|July 15, 2018
PubMed

Insights

Targeting GATA3, a key factor in ovarian cancer stemness, with the UTX inhibitor GSKJ4 shows promise. This approach enhances cancer cell death and may lead to new precision epigenetic therapies for ovarian high-grade serous carcinoma.

Area of Science:

  • Gynecologic Oncology
  • Cancer Stem Cell Biology
  • Epigenetics

Background:

  • Ovarian high-grade serous carcinoma (HGSC) is a lethal gynecological cancer.
  • Cancer stem cells drive drug resistance and recurrence in HGSC.
  • Previous attempts to target cancer stem cells have been unsuccessful.

Purpose of the Study:

  • To identify novel targets for overcoming drug resistance in HGSC.
  • To investigate the role of developmental transcription factors in HGSC stemness.
  • To explore potential therapeutic strategies targeting cancer stem cells.

Main Methods:

  • Differential transcriptome analysis of HGSC stem and progenitor cells.
  • Investigated the role of GATA3 and its interaction with UTX.
  • Utilized UTX inhibitor GSKJ4 to target GATA3-driven stemness.
  • Assessed synergistic effects of GSKJ4 with standard chemotherapies (gemcitabine, paclitaxel).

Main Results:

  • GATA3 is highly expressed in HGSC stem cells and associated with poor prognosis.
  • GATA3 recruits UTX (H3K27 demethylase), activating stemness markers.
  • GSKJ4 treatment inhibited GATA3-driven stemness and promoted apoptosis.
  • Combination therapy with GSKJ4 demonstrated synergistic cytotoxicity.

Conclusions:

  • GATA3 plays a critical role in promoting ovarian HGSC stemness.
  • Targeting the GATA3-UTX axis with GSKJ4 is a viable therapeutic strategy.
  • GATA3 may serve as a biomarker for precision epigenetic therapy in HGSC.
Keywords:
GATA3GSKJ4UTXcancer stem cellsovarian cancer

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