scholarly journals Role of Sigma-1 Receptor in Calcium Modulation: Possible Involvement in Cancer

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 139
Author(s):  
Ilaria Pontisso ◽  
Laurent Combettes
Keyword(s):  
Cell Survival ◽  
Cancer Progression ◽  
Strong Impact ◽  
Protective Function ◽  
Sigma 1 Receptor ◽  
Contact Sites ◽  
Calcium Modulation ◽  
Sigma 1 ◽  
Cancer Cell Survival

Ca2+ signaling plays a pivotal role in the control of cellular homeostasis and aberrant regulation of Ca2+ fluxes have a strong impact on cellular functioning. As a consequence of this ubiquitous role, Ca2+ signaling dysregulation is involved in the pathophysiology of multiple diseases including cancer. Indeed, multiple studies have highlighted the role of Ca2+ fluxes in all the steps of cancer progression. In particular, the transfer of Ca2+ at the ER-mitochondrial contact sites, also known as mitochondrial associated membranes (MAMs), has been shown to be crucial for cancer cell survival. One of the proteins enriched at this site is the sigma-1 receptor (S1R), a protein that has been described as a Ca2+-sensitive chaperone that exerts a protective function in cells in various ways, including the modulation of Ca2+ signaling. Interestingly, S1R is overexpressed in many types of cancer even though the exact mechanisms by which it promotes cell survival are not fully elucidated. This review summarizes the findings describing the roles of S1R in the control of Ca2+ signaling and its involvement in cancer progression.

scholarly journals mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

2018 ◽  
Vol 19 (10) ◽  
pp. 3267 ◽  
Author(s):  
Mio Harachi ◽  
Kenta Masui ◽  
Yukinori Okamura ◽  
Ryota Tsukui ◽  
Paul Mischel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Cancer Cell Survival

Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells.

scholarly journals Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Composition ◽  
Sigma 1 Receptor ◽  
Functional Roles ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Sigma 1 ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

scholarly journals Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

2015 ◽  
Vol 112 (47) ◽  
pp. E6562-E6570 ◽  
Author(s):  
Shang-Yi A. Tsai ◽  
Jian-Ying Chuang ◽  
Meng-Shan Tsai ◽  
Xiao-fei Wang ◽  
Zheng-Xiong Xi ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Envelope ◽  
Chromatin Remodeling ◽  
Behavioral Sensitization ◽  
Specific Protein ◽  
Cellular Regulation ◽  
Sigma 1 Receptor ◽  
Withdrawal Treatment ◽  
Sigma 1

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

At the Crossing of ER Stress and MAMs: A Key Role of Sigma-1 Receptor?

2019 ◽  
pp. 699-718 ◽  
Author(s):  
Benjamin Delprat ◽  
Lucie Crouzier ◽  
Tsung-Ping Su ◽  
Tangui Maurice
Keyword(s):  
Er Stress ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell Survival and Gemcitabine Resistance

Cancers ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 142 ◽  
Author(s):  
Omar Elaskalani ◽  
Marco Falasca ◽  
Niamh Moran ◽  
Michael Berndt ◽  
Pat Metharom
Keyword(s):  
Pancreatic Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Gemcitabine Resistance ◽  
Cancer Cell Survival

scholarly journals The Role of ZNF143 in Breast Cancer Cell Survival Through the NAD(P)H Quinone Dehydrogenase 1–p53–Beclin1 Axis Under Metabolic Stress

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 296 ◽  
Author(s):  
A Paek ◽  
Ji Mun ◽  
Mun Jo ◽  
Hyosun Choi ◽  
Yun Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Zinc Finger Protein ◽  
Metabolic Stress ◽  
Cancer Cell Survival ◽  
Autophagic Process ◽  
Low Expression

Autophagy is a cellular process that disrupts and uses unnecessary or malfunctioning components for cellular homeostasis. Evidence has shown a role for autophagy in tumor cell survival, but the molecular determinants that define sensitivity against autophagic regulation in cancers are not clear. Importantly, we found that breast cancer cells with low expression levels of a zinc-finger protein, ZNF143 (MCF7 sh-ZNF143), showed better survival than control cells (MCF7 sh-Control) under starvation, which was compromised with chloroquine, an autophagy inhibitor. In addition, there were more autophagic vesicles in MCF7 sh-ZNF143 cells than in MCF7 sh-Control cells, and proteins related with the autophagic process, such as Beclin1, p62, and ATGs, were altered in cells with less ZNF143. ZNF143 knockdown affected the stability of p53, which showed a dependence on MG132, a proteasome inhibitor. Data from proteome profiling in breast cancer cells with less ZNF143 suggest a role of NAD(P)H quinone dehydrogenase 1(NQO1) for p53 stability. Taken together, we showed that a subset of breast cancer cells with low expression of ZNF143 might exhibit better survival via an autophagic process by regulating the p53–Beclin1 axis, corroborating the necessity of blocking autophagy for the best therapy.

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