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

• Main Authors: Eric Owusu Obeng, Isabella Rusciano, Maria Vittoria Marvi, Antonietta Fazio, Stefano Ratti, Matilde Yung Follo, Jie Xian, Lucia Manzoli, Anna Maria Billi, Sara Mongiorgi, Giulia Ramazzotti, Lucio Cocco
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: International Journal of Molecular Sciences
• Subjects: phosphoinositides; phospholipase C; cancer; phosphatidylinositol
• Online Access: https://www.mdpi.com/1422-0067/21/7/2581
• ISSN: 1661-6596; 1422-0067

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.