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.
Highlights
Lipids, most importantly phospholipids, are the main structural constituents of all cellular membranes
About 30% of confirmed myelodysplastic syndromes (MDS) cases evolve into acute myeloid leukemia (AML), so it is imperative to identify biomolecular markers associated with the risk of AML evolution in MDS patients [86,87,88]
This review shows that phospholipase C (PLC) play a central role in the regulation of cellular signaling in cancer mechanisms
Summary
Most importantly phospholipids, are the main structural constituents of all cellular membranes. All these evidences highlight the importance of understanding how PIs and their metabolic enzymes mediate critical roles implicated in cancer. PIs form just a minor fraction of the total phospholipid content in eukaryotic cell membranes They function in diverse roles, ranging from regulating essential biological processes such as cell adhesion [7], migration [8], apoptosis [9], vesicular trafficking [10], to post-translational modifications [11]. PI levels are regulated by several lipid kinases, phosphatases and phospholipases in response to different external stimuli, with a plethora of studies showing that a deregulation of the PI metabolism mediated by these enzymes is implicated in several diseases [12,13,14] Readers can find in-depth information on the other phospholipases, i.e., PLA, PLB and PLD [15,16,17]
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