Phosphoinositide metabolism is crucial intracellular signaling system that regulates a plethora of
biological functions including mitogenesis, cell proliferation and division.
Phospholipase C gamma 1 (PLCγ1) 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 PLCγ1 is linked to a plethora of deadly human
cancers including
carcinomas of the breast, lung, pancreas, stomach, prostate and ovary. Although PLCγ1 cross-talks with many onco-drivers and signaling circuits including PI3K, AKT, HIF1-α 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 PLCG1 gene and molecular roles of PLCγ1 in several major human
cancers, a knowledgebase that can be utilized to develop novel,
isoform-specific small molecule inhibitors of PLCγ1.