Lysophosphatidic Acid Suppresses Apoptosis of High-grade Serous Ovarian Cancer Cells by Inducing Autophagy Activity and Promotes Cell-cycle Progression EGFR-PI3K/Aurora-A-geminin Dual Signaling Pathways

Overview

Journal Front Pharmacol

Date 2023 Jan 5

PMID 36601056

Authors

Haile Zhao

Peijun Jia

Kathleen Nanding

Man Wu

Xiaozhou Bai

Morigen Morigen

Lifei Fan

Affiliations

Soon will be listed here.

Abstract

Lysophosphatidic acid (LPA) and geminin are overexpressed in ovarian cancer, and increasing evidence supports their contribution to ovarian tumor development. Here, we reveal that geminin depletion induces autophagy suppression and enhances reactive oxygen species (ROS) production and apoptosis of high-grade serous ovarian cancer (HGSOC) cells. Bioinformatics analysis and pharmacological inhibition studies confirm that LPA activates geminin expression in the early S phase in HGSOC cells the LPAR/MMPs/EGFR/PI3K/mTOR pathway. Furthermore, LPA phosphorylates Aurora-A kinase on Thr288 through EGFR transactivation, and this event potentiates additional geminin stabilization. In turn, overexpressed and stabilized geminin regulates DNA replication, cell-cycle progression, and cell proliferation of HGSOC cells. Our data provide potential targets for enhancing the clinical benefit of HGSOC precision medicine.

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