Jin Yue, Xue Jian, Li Xinyue, Zhong Xiaoli
Department of Medical Research Center, Northern Jiangsu People's Hospital, Jiangsu, Yangzhou, 225001, PR China.
Department of Emergency Medicine, Yizheng People's Hospital, Jiangsu, Yangzhou, 211400, PR China.
Transl Oncol. 2025 Jul;57:102420. doi: 10.1016/j.tranon.2025.102420. Epub 2025 May 19.
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.
近年来，磷酸肌醇信号通路因其与包括乳腺癌在内的各种人类疾病相关的代谢改变有关而备受关注。磷脂酰肌醇-5-磷酸4-激酶（PIP4K）催化磷脂酰肌醇-5-磷酸（PI5P）磷酸化生成磷脂酰肌醇-4,5-二磷酸（PI(4,5)P2），这是一种调节与癌细胞生长和转移相关信号通路的脂质。在乳腺癌中，PIP4K，尤其是PIP4Kα和PIP4Kβ，已成为一个重要因素，它们的失调与肿瘤进展和不良预后有关。然而，PIP4K家族的另一种异构体PIP4Kγ（由PIP4K2C编码）在乳腺癌中的作用在很大程度上仍不清楚。在这里，我们利用GTEx和TCGA公共数据库证明，与正常组织相比，PIP4K2C在乳腺癌组织中的表达上调。PIP4K2C表达的升高在乳腺癌细胞系和组织中得到进一步证实。通过siRNA下调PIP4K2C的表达降低了亚细胞PI(4,5)P2水平，并抑制了MDA-MB-468、MCF7乳腺癌细胞系的增殖、迁移和侵袭。我们的研究证实PIP4K2C是一种有前景的乳腺癌诊断和治疗生物标志物，值得进一步研究其机制和临床意义。
