ArticleMolecular pharmacology2013
Sequential cytoprotective responses to Sigma1 ligand-induced endoplasmic reticulum stress.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- The Role of Sigmar1 in Autophagy Regulation and Disease Therapy.International journal of molecular sciences · 2026Review
- Sigma-1 Receptor Ligands for CNS Cancer Treatment.CNS drugs · 2025Review
- Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.Cancer biology & therapy · 2025Article
- Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.ACS pharmacology & translational science · 2025Review
- Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.Future medicinal chemistry · 2024Review
- Sigma1 Regulates Lipid Droplet-mediated Redox Homeostasis Required for Prostate Cancer Proliferation.Cancer research communications · 2023Article
- Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer.Journal of cellular and molecular medicine · 2023Review
- Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.Metabolites · 2022Review
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.Journal of medicinal chemistry · 2021Review
- Review
- Article
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- Enhanced Affinity for 3-Amino-Chromane-Derived σACS omega · 2020Article
- Article
- Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using (Molecules (Basel, Switzerland) · 2020Article
- Haloperidol and Prostate Cancer Prevention: More Epidemiologic Research Needed.The Permanente journal · 2020Article
- Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?Frontiers in pharmacology · 2020Review
- Acute Toxic Injuries of Rat's Visceral Tissues Induced by Different Oximes.Scientific reports · 2019Article
- 3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HTACS medicinal chemistry letters · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The Sigma1 receptor (Sigma1) is an endoplasmic reticulum (ER) integral membrane protein that is highly expressed in a number of cancer cell lines. Small molecule compounds targeting Sigma1 (Sigma1 ligands) inhibit cancer cell proliferation and induce apoptotic cell death in vitro and inhibit tumor growth in xenograft experiments. However, the cellular pathways activated by Sigma1 protein-ligand interaction are not well defined. Here, we find that treatment with some Sigma1 ligands induces ER stress and activates the unfolded protein response (UPR) in a dose- and time-responsive manner in a range of adenocarcinoma cell lines. Autophagy is engaged after extended treatment with Sigma1 ligands, which suggests that protracted UPR results in autophagy as a secondary response. Inhibition of UPR by RNAi-mediated knockdown of inositol-requiring enzyme 1α and activating transcription factor 4 abrogates autophagosome formation, as does knockdown of essential autophagy gene products Beclin1 and autophagy protein 5. Knockdown of Sigma1 also suppresses IPAG [1-(4-iodophenyl)-3-(2-adamantyl) guanidine] induced UPR marker and autophagosome levels, indicating that this response is indeed Sigma1-mediated. We find that UPR activation precedes autophagosome formation and autophagy precedes apoptosis in Sigma1 ligand-treated cells. These processes are reversible, and washout of IPAG before cell death results in a return of autophagosomes and UPR markers toward basal levels. However, inhibition of Sigma1 ligand-induced UPR or autophagy accelerates apoptotic cell death. Together, these data suggest that UPR and autophagy are engaged as primary and secondary cytoprotective responses, respectively, to Sigma1 ligand-induced disruption of cancer cell protein homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.