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Objective <p>Ovarian cancer is the eighth most common malignancy among women worldwide. Despite advances in treatment, chemoresistance and associated morbidity remain significant challenges. This study aims to elucidate the role of acetate-dependent acetyl-CoA synthetase 2 (ACSS2) in ovarian cancer progression under hypoxic conditions, identifying its potential as a therapeutic target.</p> Results <p>Immunohistochemistry revealed that ACSS2 was overexpressed and predominantly localized to the nucleus in High-Grade Serous Ovarian Carcinoma (HGSOC) tissues, with significantly higher H-scores compared to low-grade and normal tissues. Functional assays conducted on ovarian cancer cell lines (Skov-3 and PA-1) demonstrated that ACSS2 inhibition reduced proliferation, colony formation, and three-dimensional spheroid growth, with greater sensitivity observed under hypoxic conditions. Migration and invasion assays further indicated that ACSS2 inhibition significantly impaired cellular motility and invasiveness, particularly in hypoxia. Mechanistic studies, including Western blotting and RT-qPCR, showed that ACSS2 inhibition modulated the PI3K pathway and downregulated Hypoxia-Inducible Factor 2 (HIF-2) levels as well as HIF-2-responsive genes expression under hypoxic conditions. These findings highlight the role of ACSS2 in metabolic adaptation, tumor progression, and its potential as a biomarker and therapeutic target in ovarian cancer.</p> Conclusions <p>ACSS2 is a critical regulator of ovarian cancer growth and invasiveness under hypoxic stress. Targeting ACSS2 may represent a promising therapeutic strategy for managing ovarian cancer. Further studies are warranted to explore its clinical potential.</p>

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ACSS2 promotes proliferation and invasiveness of SKOV-3 and PA-1 ovarian cancer cell lines under hypoxia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • Ola Mroweh,
  • Louna Karam,
  • Razane Hammoud,
  • Jana Al Achcar,
  • Rania Sobh,
  • Selim M. Nasser,
  • Joseph A. Garcia,
  • Philippe Hussein Kobeissy

摘要

Objective

Ovarian cancer is the eighth most common malignancy among women worldwide. Despite advances in treatment, chemoresistance and associated morbidity remain significant challenges. This study aims to elucidate the role of acetate-dependent acetyl-CoA synthetase 2 (ACSS2) in ovarian cancer progression under hypoxic conditions, identifying its potential as a therapeutic target.

Results

Immunohistochemistry revealed that ACSS2 was overexpressed and predominantly localized to the nucleus in High-Grade Serous Ovarian Carcinoma (HGSOC) tissues, with significantly higher H-scores compared to low-grade and normal tissues. Functional assays conducted on ovarian cancer cell lines (Skov-3 and PA-1) demonstrated that ACSS2 inhibition reduced proliferation, colony formation, and three-dimensional spheroid growth, with greater sensitivity observed under hypoxic conditions. Migration and invasion assays further indicated that ACSS2 inhibition significantly impaired cellular motility and invasiveness, particularly in hypoxia. Mechanistic studies, including Western blotting and RT-qPCR, showed that ACSS2 inhibition modulated the PI3K pathway and downregulated Hypoxia-Inducible Factor 2 (HIF-2) levels as well as HIF-2-responsive genes expression under hypoxic conditions. These findings highlight the role of ACSS2 in metabolic adaptation, tumor progression, and its potential as a biomarker and therapeutic target in ovarian cancer.

Conclusions

ACSS2 is a critical regulator of ovarian cancer growth and invasiveness under hypoxic stress. Targeting ACSS2 may represent a promising therapeutic strategy for managing ovarian cancer. Further studies are warranted to explore its clinical potential.