An investigation of Sigma-1 receptor expression and ligand-induced endoplasmic reticulum stress in breast cancer

Borde, Preeti; Cosgrove, Nicola; Charmsaz, Sara; Safrany, Stephen T.; Young, Leonie S.

doi:10.1038/s41417-022-00552-4

Cited by 3 publications

(4 citation statements)

References 44 publications

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“…SigmaR1 has been found to be upregulated in a number of cancers including lung cancer, breast cancer, glioblastoma, esophageal cancer, pancreatic cancer, prostate cancer, and liver cancer [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Several studies showed that SigmaR1 is highly expressed both at the gene and protein levels in breast cancer patient tissues and is associated with a worse prognosis and poor survival outcomes [ 33 , 39 , 40 ]. Whether this association represents a correlation, or a causality is still awaiting mechanistic studies.…”

Section: The Role Of Sigmar1 In Breast Cancermentioning

confidence: 99%

“…Whether this association represents a correlation, or a causality is still awaiting mechanistic studies. Of these studies, Borde et al indicated that not only was SigmaR1 upregulated in breast cancer cell lines, but it was especially upregulated in triple-negative breast cancer cell lines [ 40 ]. An earlier study of 95 patients with operable primary breast cancers by Simony-Lafontaine et al [ 39 ] reported a link between SigmaR1 and human sterol isomerase (hSI).…”

Section: The Role Of Sigmar1 In Breast Cancermentioning

confidence: 99%

“…Other SigmaR1 antagonists have also been studied for cancer cell inhibition. A recent study by Borde et al, reported that treatment in different breast cancer cell lines, including a high SigmaR1 expressing TNBC and an estrogen receptor (ER) + (low-SigmaR1 expressing) with the SigmaR1 antagonist 1-(4-iodophenyl)-3-(2-adamantyl)guanidine (IPAG) activated the UPR in both cell lines and caused aggregation and colocalization of the receptor with the ER-stress marker binding immunoglobulin protein (BiP) in the tamoxifen-resistant LY2 cells [ 40 ]. Oflaz et al used single-cell fluorescence microscopy to evaluate real-time ion and metabolic fluxes in A549 lung adenocarcinoma and MC57 breast cancer cell lines [ 73 ].…”

Section: Towards Targeting Sigmar1 In Breast Cancermentioning

confidence: 99%

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An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer

Robinson

Osman

2023

Cancers

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Despite the major progress in treating breast cancer, recurrence remains a problem and types such as triple-negative breast cancer still lack targeted medicine. The orphan Sigma receptor1 (SigmaR1) has emerged as a target in breast cancer, but its mechanism of action is unclear and hinders clinical utility. SigmaR1 is widely expressed in organ tissues and localized to various sub-cellular compartments, particularly the endoplasmic reticulum (ER), the mitochondrial-associated membranes (MAMs) and the nuclear envelope. As such, it involves diverse cellular functions, including protein quality control/ER stress, calcium signaling, cholesterol homeostasis, mitochondrial integrity and energy metabolism. Consequently, SigmaR1 has been implicated in a number of cancers and degenerative diseases and thus has been intensively pursued as a therapeutic target. Because SigmaR1 binds a number of structurally unrelated ligands, it presents an excellent context-dependent therapeutic target. Here, we review its role in breast cancer and the current therapies that have been considered based on its known functions. As SigmaR1 is not classified as an oncoprotein, we propose a model in which it serves as an oligomerization adaptor in key cellular pathways, which may help illuminate its association with variable diseases and pave the way for clinical utility in personalized medicine.

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Section: The Role Of Sigmar1 In Breast Cancermentioning

confidence: 99%

Section: The Role Of Sigmar1 In Breast Cancermentioning

confidence: 99%

Section: Towards Targeting Sigmar1 In Breast Cancermentioning

confidence: 99%

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An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer

Robinson

Osman

2023

Cancers

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“…However, it appears more concentrated in the central nervous system (CNS), heart, liver and eyes [ 17 , 18 ]. Many cancers also overexpress the σ1R, suggesting that the σ1R plays an important role in cell survival under stressful conditions [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

Malar,

Thitilertdecha,

Ruckvongacheep

et al. 2023

CNS Drugs

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The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.

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Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells

Yıldız,

Demirel,

Havadar

et al. 2023

Biol Trace Elem Res

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An investigation of Sigma-1 receptor expression and ligand-induced endoplasmic reticulum stress in breast cancer

Cited by 3 publications

References 44 publications

An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer

An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer

Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells

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