Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur Campus, Tamil Nadu, Chennai 603203, India.
Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur Campus, Tamil Nadu, Chennai 603203, India.
Endocr Metab Immune Disord Drug Targets. 2022;22(6):601-611. doi: 10.2174/1871530321666211130145542.
Progesterone receptor membrane component 1 (PGRMC1) is a trans-membrane evolutionarily conserved protein with a cytochrome b5 like heme/steroid binding domain. PGRMC1 clinical levels are strongly suggested to correlate with poor patient survival and lung cancer prognosis. PGRMC1 has been reported to possess pleiotropic functions, such as participating in cellular and membrane trafficking, steroid hormone signaling, cholesterol metabolism and steroidogenesis, glycolysis and mitochondrial energy metabolism, heme transport and homeostasis, neuronal movement and synaptic function, autophagy, anti-apoptosis, stem cell survival and the list is still expanding. PGRMC1 mediates its pleiotropic functions through its ability to interact with multiple binding partners, such as epidermal growth factor receptor (EGFR), sterol regulatory element binding protein cleavage activating protein (SCAP), insulin induced gene-1 protein (Insig-1), heme binding proteins (hepcidin, ferrochelatase and cyp450 members), plasminogen activator inhibitor 1 RNA binding protein (PAIR-BP1). In this review, we provide a comprehensive overview of PGRMC1 and its associated pleiotropic functions that are indispensable for lung cancer promotion and progression, suggesting it as a prospective therapeutic target for intervention. Notably, we have compiled and reported various preclinical studies wherein prospective agonists and antagonists had been tested against PGRMC1 expressing cancer cell lines, suggesting it as a prospective therapeutic target for cancer intervention.
孕激素受体膜成分 1（PGRMC1）是一种跨膜进化上保守的蛋白，具有细胞色素 b5 样血红素/甾体结合域。PGRMC1 的临床水平强烈提示与患者生存不良和肺癌预后相关。据报道，PGRMC1 具有多种功能，如参与细胞和膜运输、甾体激素信号转导、胆固醇代谢和甾体生成、糖酵解和线粒体能量代谢、血红素转运和动态平衡、神经元运动和突触功能、自噬、抗细胞凋亡、干细胞存活等，而且这个列表还在不断扩大。PGRMC1 通过与多种结合伴侣相互作用来介导其多种功能，如表皮生长因子受体（EGFR）、固醇调节元件结合蛋白裂解激活蛋白（SCAP）、胰岛素诱导基因-1 蛋白（Insig-1）、血红素结合蛋白（hepcidin、亚铁螯合酶和 CYP450 成员）、纤维蛋白溶酶原激活物抑制剂 1 RNA 结合蛋白（PAIR-BP1）。在这篇综述中，我们全面概述了 PGRMC1 及其相关的多效性功能，这些功能对于肺癌的促进和进展是不可或缺的，表明它是一种有前途的治疗干预靶点。值得注意的是，我们已经编译并报告了各种临床前研究，其中已经针对表达 PGRMC1 的癌细胞系测试了潜在的激动剂和拮抗剂，表明它是癌症干预的一个有前途的治疗靶点。
