School of Pharmacy, Guangdong Medical College, 1 Xincheng Ave, Songshan Lake Technology Park, Dongguan, Guangdong, 523808, China.
Med Res Rev. 2014 May;34(3):532-66. doi: 10.1002/med.21297. Epub 2013 Aug 6.
The sigma-2 receptor is highly expressed in various rapidly proliferating cancer cells and regarded as a cancer cell biomarker. Selective sigma-2 ligands have been shown to specifically label the tumor sites, induce cancer cells to undergo apoptosis, and inhibit tumor growth. Sigma-2 ligands are potentially useful as cancer diagnostics, anticancer therapeutics, or adjuvant anticancer treatment agents. However, both the cloning of this receptor and the identification of its endogenous ligand have not been successful, and the lack of structural information has severely hindered the understanding of its physiological roles, its signaling pathways, and the development of more selective sigma-2 ligands. Recent data have implicated that sigma-2 binding sites are within the lipid rafts and that PGRMC1 (progesterone receptor membrane component 1) complex and sigma-2 receptor may be coupled with EGFR (epidermal growth factor receptor), mTOR (mammalian target of rapamycin), caspases, and ion channels. Due to its promising applications in cancer management, there are rapidly increasing research efforts that are being directed into this field. This review article updates the current understanding of sigma-2 receptor and its potential physiological roles, applications, interaction with other effectors, with special focuses on the development of sigma-2 ligands, their chemical structures, pharmacological profiles, applications in imaging and anticancer therapy.
sigma-2 受体在各种快速增殖的癌细胞中高度表达，被认为是一种癌细胞生物标志物。选择性 sigma-2 配体已被证明可特异性标记肿瘤部位，诱导癌细胞凋亡，并抑制肿瘤生长。sigma-2 配体有望作为癌症诊断、抗癌治疗或辅助抗癌治疗剂。然而，该受体的克隆和内源性配体的鉴定都没有成功，并且缺乏结构信息严重阻碍了对其生理作用、信号通路以及更具选择性的 sigma-2 配体的开发的理解。最近的数据表明，sigma-2 结合位点位于脂筏内，PGRMC1（孕激素受体膜成分 1）复合物和 sigma-2 受体可能与 EGFR（表皮生长因子受体）、mTOR（雷帕霉素的哺乳动物靶标）、半胱天冬酶和离子通道偶联。由于其在癌症管理中的应用前景广阔，目前针对这一领域的研究正在迅速增加。本文综述了 sigma-2 受体及其潜在生理作用、应用、与其他效应物相互作用的最新研究进展，特别关注 sigma-2 配体的开发、它们的化学结构、药理学特性、在成像和抗癌治疗中的应用。
