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LCP1 promotes ovarian cancer cell resistance to olaparib by activating the JAK2/STAT3 signalling pathway

Minxue Gai1, Lanlan Zhao2, Hongqi Li2

  • 1Medical Integration and Practice Center, Shandong University, Jinan, Shandong, China.

Cancer Biology & Therapy
|November 26, 2024
PubMed
Abstract

Insights

Lymphocyte cytosolic protein 1 (LCP1) drives resistance to olaparib in ovarian cancer by activating JAK2/STAT3 and EMT pathways. Targeting LCP1 may overcome treatment resistance in ovarian cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Poly (ADP-ribose) polymerase inhibitors (PARPis) are crucial in ovarian cancer (OC) treatment, but resistance is a significant challenge.
  • The mechanisms underlying PARPi resistance in OC are not fully understood.
  • Lymphocyte cytosolic protein 1 (LCP1) is implicated in tumor progression, while the JAK2/STAT3 pathway influences metastasis and chemoresistance via epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of LCP1 in olaparib resistance in ovarian cancer.
  • To elucidate the underlying molecular mechanisms, including the involvement of the JAK2/STAT3 pathway and EMT.

Main Methods:

  • Established an olaparib-resistant ovarian cancer cell line.
  • Utilized cell survival, Transwell, colony formation, western blotting, and flow cytometry assays.
  • Performed RNA sequencing to identify genes associated with olaparib resistance.

Main Results:

  • LCP1 was significantly overexpressed in olaparib-resistant OC cells compared to parental cells.
  • Overexpression of LCP1 enhanced olaparib resistance, while LCP1 knockdown attenuated it.
  • Upregulation of LCP1 correlated with increased activity of the JAK2/STAT3 pathway and elevated levels of EMT markers.

Conclusions:

  • LCP1 plays a critical role in mediating olaparib resistance in ovarian cancer by activating the JAK2/STAT3 signaling pathway and promoting EMT.
  • LCP1 represents a potential therapeutic target for overcoming olaparib resistance in ovarian cancer.
  • This study reveals a novel mechanism contributing to olaparib resistance in ovarian cancer.
Keywords:
EMT6JAK2/STAT35LCP14PARPi1ovarian cancer3resistance2

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