Downregulation of PIP4K2C inhibits the breast cancer cell proliferation, migration and invasion.

Phosphoinositide signaling pathway has garnered significant attention in recent years due to its implication in metabolic alterations associated with various human diseases, including breast cancer. Phosphatidylinositol-5-phosphate 4-kinase (PIP4K) catalyzes the phosphorylation of phosphatidylinositol-5-phosphate (PI5P) to produce phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a lipid that regulates signaling pathways associated with cancer cell growth and metastasis. In breast cancer, PIP4Ks, especially PIP4Kα and PIP4Kβ, have emerged as a significant player, with their dysregulation linked to tumor progression and poor prognosis. However, the role of PIP4Kγ (encoded by PIP4K2C), the other isoform of PIP4K family, remains largely uncharted in breast cancer. Here, we demonstrated that the expression of PIP4K2C is upregulated in breast cancer tissues opposed to the normal tissue utilizing the GTEx and the TCGA public database. The elevation of PIP4K2C expression is further confirmed in the breast cancer cell lines and tissues. Downregulated expression of PIP4K2C by siRNA lowered the subcellular PI(4,5)P2 and suppressed proliferation, migration and invasion of MDA-MB-468, MCF7 breast cancer cell lines. Our research substantiates PIP4K2C as a promising diagnostic and therapeutic biomarker for breast cancer, warranting further investigation into its mechanistic and clinical implications.