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Lipid droplet-associated hydrolase (LDAH) knockdown enhances TAG hydrolysis and promotes ovarian cancer progression and chemoresistance

  • 0Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY, USA.
Oncogenesis +

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July 2, 2025

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July 2, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Ovarian cancer cells reduce lipid droplet-associated hydrolase (LDAH) to promote tumor growth and chemoresistance. This involves increased activity of adipose triglyceride lipase (ATGL), leading to poor patient survival.

Area Of Science

  • Biochemistry
  • Oncology
  • Cell Biology

Background

  • Lipid droplet-associated hydrolase (LDAH) is a lipid hydrolase found in adipose and ovarian tissues.
  • LDAH's role in ovarian cancer progression and chemoresistance remains largely unexplored.
  • Decreased LDAH expression correlates with advanced ovarian cancer stages and poorer patient survival.

Purpose Of The Study

  • To investigate the function of LDAH in ovarian cancer.
  • To determine the relationship between LDAH expression, tumor growth, and chemoresistance.
  • To elucidate the molecular mechanisms underlying LDAH's role in ovarian cancer.

Main Methods

  • Analysis of patient datasets for LDAH expression and survival correlation.
  • In vitro studies involving LDAH knockdown in ovarian cancer cell lines.
  • Xenograft mouse models to assess tumor growth and response to cisplatin treatment.
  • Investigation of lipid droplet content, triacylglycerol (TAG) hydrolysis, and key protein expressions (ATGL, CPT1A, NF-kB).

Main Results

  • LDAH knockdown in ovarian cancer cells increased proliferation, tumor growth, and cisplatin resistance.
  • LDAH knockdown led to smaller lipid droplets, decreased TAG, and increased adipose triglyceride lipase (ATGL) expression.
  • Increased ATGL expression correlated with chemoresistance and shorter patient survival.
  • ATGL inhibition attenuated the pro-tumorigenic and chemoresistant phenotype in LDAH-deficient cells.

Conclusions

  • Ovarian cancer cells downregulate LDAH, promoting tumor growth and chemoresistance.
  • This downregulation enhances ATGL-mediated TAG hydrolysis, contributing to increased tumor progression.
  • LDAH and ATGL represent potential therapeutic targets for ovarian cancer treatment.