Zeng Chenbo, Riad Aladdin, Mach Robert H
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancers (Basel). 2020 Jul 13;12(7):1877. doi: 10.3390/cancers12071877.
The sigma-2 receptor was originally defined pharmacologically and recently identified as TMEM97. TMEM97 has been validated as a biomarker of proliferative status and the radioligand of TMEM97, [F]ISO-1, has been developed and validated as a PET imaging biomarker of proliferative status of tumors and as a predictor of the cancer therapy response. [F]ISO-1 PET imaging should be useful to guide treatment for cancer patients. TMEM97 is a membrane-bound protein and localizes in multiple subcellular organelles including endoplasmic reticulum and lysosomes. TMEM97 plays distinct roles in cancer. It is reported that TMEM97 is upregulated in some tumors but downregulated in other tumors and it is required for cell proliferation in certain tumor cells. TMEM97 plays important roles in cholesterol homeostasis. TMEM97 expression is regulated by cholesterol-regulating signals such as sterol depletion and SREBP expression levels. TMEM97 regulates cholesterol trafficking processes such as low density lipoprotein (LDL) uptake by forming complexes with PGRMC1 and low density lipoprotein receptor (LDLR), as well as cholesterol transport out of lysosome by interacting with and regulating NPC1 protein. Understanding molecular functions of TMEM97 in proliferation and cholesterol metabolism will be important to develop strategies to diagnose and treat cancer and cholesterol disorders using a rich collection of TMEM97 radiotracers and ligands.
σ-2受体最初是通过药理学定义的，最近被鉴定为跨膜蛋白97（TMEM97）。TMEM97已被确认为增殖状态的生物标志物，其放射性配体[F]ISO-1已被开发并验证为肿瘤增殖状态的正电子发射断层显像（PET）成像生物标志物以及癌症治疗反应的预测指标。[F]ISO-1 PET成像应有助于指导癌症患者的治疗。TMEM97是一种膜结合蛋白，定位于包括内质网和溶酶体在内的多个亚细胞细胞器中。TMEM97在癌症中发挥着不同的作用。据报道，TMEM97在某些肿瘤中上调，但在其他肿瘤中下调，并且在某些肿瘤细胞的细胞增殖中是必需的。TMEM97在胆固醇稳态中起重要作用。TMEM97的表达受胆固醇调节信号如甾醇耗竭和固醇调节元件结合蛋白（SREBP）表达水平的调控。TMEM97通过与孕激素受体膜组分1（PGRMC1）和低密度脂蛋白受体（LDLR）形成复合物来调节胆固醇转运过程，如低密度脂蛋白（LDL）摄取，以及通过与NPC1蛋白相互作用并调节其功能来促进胆固醇从溶酶体中转运出来。了解TMEM97在增殖和胆固醇代谢中的分子功能对于利用丰富的TMEM97放射性示踪剂和配体开发诊断和治疗癌症及胆固醇紊乱的策略至关重要。
