Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

Author:

Owusu Obeng EricORCID,Rusciano Isabella,Marvi Maria Vittoria,Fazio Antonietta,Ratti StefanoORCID,Follo Matilde Yung,Xian Jie,Manzoli Lucia,Billi Anna MariaORCID,Mongiorgi Sara,Ramazzotti GiuliaORCID,Cocco Lucio

Abstract

Phosphoinositides (PI) form just a minor portion of the total phospholipid content in cells but are significantly involved in cancer development and progression. In several cancer types, phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] play significant roles in regulating survival, proliferation, invasion, and growth of cancer cells. Phosphoinositide-specific phospholipase C (PLC) catalyze the generation of the essential second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (InsP3) by hydrolyzing PtdIns(4,5)P2. DAG and InsP3 regulate Protein Kinase C (PKC) activation and the release of calcium ions (Ca2+) into the cytosol, respectively. This event leads to the control of several important biological processes implicated in cancer. PLCs have been extensively studied in cancer but their regulatory roles in the oncogenic process are not fully understood. This review aims to provide up-to-date knowledge on the involvement of PLCs in cancer. We focus specifically on PLCβ, PLCγ, PLCδ, and PLCε isoforms due to the numerous evidence of their involvement in various cancer types.

Funder

Fondazione Cassa di Risparmio di Bologna

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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