ArticleOncogene2013
mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 36 citations in OpenAlex.
- Onychomatricoma with Tuberous Sclerosis: A Novel Association?Indian dermatology online journal · 2026Article
- Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025Review
- The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington's Disease and Other Human Pathologies.International journal of molecular sciences · 2022Review
- Review
- Ablation of collagen VI leads to the release of platelets with altered function.Blood advances · 2021Article
- p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth.EMBO reports · 2021Article
- CHD1L prevents lipopolysaccharide-induced hepatocellular carcinomar cell death by activating hnRNP A2/B1-nmMYLK axis.Cell death & disease · 2021Article
- Review
- Review
- Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development.Oncotarget · 2017Article
- Hyperactivated mTORC1 downregulation of FOXO3a/PDGFRα/AKT cascade restrains tuberous sclerosis complex-associated tumor development.Oncotarget · 2017Article
- Negative regulation of Smad1 pathway and collagen IV expression by store-operated CaAmerican journal of physiology. Renal physiology · 2017Article
- Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/CaScientific reports · 2017Article
- Article
- Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway.Molecular carcinogenesis · 2016Article
- Store-operated calcium entry and diabetic complications.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- Store-Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression.Journal of the American Society of Nephrology : JASN · 2015Article
- Brain-expressed X-linked 2 Is Pivotal for Hyperactive Mechanistic Target of Rapamycin (mTOR)-mediated Tumorigenesis.The Journal of biological chemistry · 2015Article
- STIM and Orai proteins as novel targets for cancer therapy. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.American journal of physiology. Cell physiology · 2015Review
- STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer.Scientific reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The protein complex of tuberous sclerosis complex (TSC)1 and TSC2 tumor suppressors is a key negative regulator of mammalian target of rapamycin (mTOR). Hyperactive mTOR signaling due to the loss-of-function of mutations in either TSC1 or TSC2 gene causes TSC, an autosomal dominant disorder featured with benign tumors in multiple organs. As the ubiquitous second messenger calcium (Ca(2+)) regulates various cellular processes involved in tumorigenesis, we explored the potential role of mTOR in modulation of cellular Ca(2+) homeostasis, and in turn the effect of Ca(2+) signaling in TSC-related tumor development. We found that loss of Tsc2 potentiated store-operated Ca(2+) entry (SOCE) in an mTOR complex 1 (mTORC1)-dependent way. The endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1), was upregulated in Tsc2-deficient cells, and was suppressed by mTORC1 inhibitor rapamycin. In addition, SOCE repressed AKT1 phosphorylation. Blocking SOCE either by depleting STIM1 or ectopically expressing dominant-negative Orai1 accelerated TSC-related tumor development, likely because of restored AKT1 activity and enhanced tumor angiogenesis. Our data, therefore, suggest that mTORC1 enhancement of store-operated Ca(2+) signaling hinders TSC-related tumor growth through suppression of AKT1 signaling. The augmented SOCE by hyperactive mTORC1-STIM1 cascade may contribute to the benign nature of TSC-related tumors. Application of SOCE agonists could thus be a contraindication for TSC patients. In contrast, SOCE agonists should attenuate mTOR inhibitors-mediated AKT reactivation and consequently potentiate their efficacy in the treatment of the patients with TSC.
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.