Recent advances in understanding the molecular role of phosphoinositide-specific phospholipase C gamma 1 as an emerging onto-driver and novel therapeutic target in human carcinogenesis

Phosphoinositide metabolism is crucial intracellular signaling system that regulates a plethora of biological functions including mitogenesis, cell proliferation and division. Phospholipase C gamma 1 (PLC gamma 1) which belongs to phosphoinositide-specific phospholipase C (PLC) family, is activated by many extracellular stimuli including hormones, neurotransmitters, growth factors and modulates several cellular and physiological functions necessary for tumorigenesis such as cell survival, migration, invasion and angiogenesis by generating inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) via hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2). Cancer remains as a leading cause of global mortality and aberrant expression and regulation of PLC gamma 1 is linked to a plethora of deadly human cancers including carcinomas of the breast, lung, pancreas, stomach, prostate and ovary. Although PLC gamma 1 cross-talks with many onco-drivers and signaling circuits including PI3K, AKT, HIF1-alpha and RAF/MEK/ERK cascade, its precise role in carcinogenesis is not completely understood. This review comprehensively discussed the status quo of this ubiquitously expressed phospholipase as a tumor driver and highlighted its significance as a novel therapeutic target in cancer. Furthermore, we have highlighted the significance of somatic driver mutations in PLCGI gene and molecular roles of PLC gamma 1 in several major human cancers, a knowledgebase that can be utilized to develop novel, isoform-specific small molecule inhibitors of PLC gamma 1.

Automated summary

Phosphoinositide metabolism is a critical intracellular signaling system that regulates various biological functions, and PLCγ1, as a member of the PLC family, plays a crucial role in tumorigenesis by modulating cell survival, migration, invasion, and angiogenesis. The aberrant expression and regulation of PLCγ1 are linked to a range of deadly human cancers, highlighting its significance as a potential therapeutic target in cancer research. Further studies are needed to fully understand PLCγ1's precise role in carcinogenesis and its potential as a novel treatment target.