The Biological Function of Sigma-2 Receptor/TMEM97 and Its Utility in PET Imaging Studies in Cancer

Cancers
Chenbo ZengRobert H Mach

Abstract

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, [18F]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. [18F]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 TMEM9...Continue Reading

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Citations

Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kai YangTaolei Sun
Feb 18, 2021·Molecular Biology of the Cell·Janina LaborenzJohannes M Herrmann
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Jun 3, 2021·Journal of Medicinal Chemistry·Antonino N FallicaSebastiano Intagliata
Jul 22, 2021·Bioorganic Chemistry·Zahra ShaghaghiSaeed Emami

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Methods Mentioned

BETA
flow cytometry
xenografts
confocal microscopy
RNAseq
proximity ligation assay

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