ArticlePloS one2016
Compensatory Increase of Transglutaminase 2 Is Responsible for Resistance to mTOR Inhibitor Treatment.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 26 citations in OpenAlex.
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Anti-inflammatory 25(OH)DCell death & disease · 2025Article
- Identification of transglutaminase 2 mediated polyaminated proteins in a hepatocellular cancer cell line.Computational and structural biotechnology journal · 2025Article
- Suppression of Ah Receptor (AhR) increases the aggressiveness of TNBC cells and 11-Cl-BBQ-activated AhR inhibits their growth.Biochemical pharmacology · 2023Article
- The transglutaminase 2 cancer cell survival factor maintains mTOR activity to drive an aggressive cancer phenotype.Molecular carcinogenesis · 2023Article
- Inhibition of the lncRNA Coded within Transglutaminase 2 Gene Impacts Several Relevant Networks in MCF-7 Breast Cancer Cells.Non-coding RNA · 2021Article
- The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment.Cancers · 2021Review
- Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment.Journal of experimental & clinical cancer research : CR · 2021Article
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- A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2.International journal of molecular sciences · 2020Review
- Expression of concern: Compensatory increase of transglutaminase 2 is responsible for resistance to mTOR inhibitor treatment.PloS one · 2020Article
- Crebl2 regulates cell metabolism in muscle and liver cells.Scientific reports · 2019Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.Molecular carcinogenesis · 2019Article
- Transglutaminase 2 Promotes Autophagy by LC3 Induction through p53 Depletion in Cancer Cell.Biomolecules & therapeutics · 2019Article
- Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma.Cell adhesion & migration · 2018Article
- mTOR function and therapeutic targeting in breast cancer.American journal of cancer research · 2017Review
Corrections and comments
- Expression of concern · 2020-01-15Contamination of Cell Lines/Tissues · Duplication of/in Image · Unreliable Results and/or Conclusions ·
- Expression of concern
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) plays a crucial role in controlling cell growth and homeostasis. Deregulation of mTOR signaling is frequently observed in some cancers, making it an attractive drug target for cancer therapy. Although mTORC1 inhibitor rapalog-based therapy has shown positive results in various pre-clinical animal cancer studies, tumors rebound upon treatment discontinuation. Moreover, several recent clinical trials showed that the mTORC1 inhibitors rapamycin and rapalog only reduce the capacity for cell proliferation without promoting cell death, consistent with the concept that rapamycin is cytostatic and reduces disease progression but is not cytotoxic. It is imperative that rapamycin-regulated events and additional targets for more effective drug combinations be identified. Here, we report that rapamycin treatment promotes a compensatory increase in transglutaminase 2 (TGM2) levels in mTORC1-driven tumors. TGM2 inhibition potently sensitizes mTORC1-hyperactive cancer cells to rapamycin treatment, and a rapamycin-induced autophagy blockade inhibits the compensatory TGM2 upregulation. More importantly, tumor regression was observed in MCF-7-xenograft tumor-bearing mice treated with both mTORC1 and TGM2 inhibitors compared with those treated with either a single inhibitor or the vehicle control. These results demonstrate a critical role for the compensatory increase in transglutaminase 2 levels in promoting mTORC1 inhibitor resistance and suggest that rational combination therapy may potentially suppress cancer therapy resistance.
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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.