ArticleMolecular and cellular biology2016
Calpain Genetic Disruption and HSP90 Inhibition Combine To Attenuate Mammary Tumorigenesis.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 25 citations in OpenAlex.
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Using fibre photometry with a fluorescence resonance energy transfer-based biosensor to test efficacy of calpain inhibitorsBrain communications · 2026Article
- Genetic disruption ofmicroPublication biology · 2026Article
- Article
- Co-Expression of MHC-II and ANXA1: Mediators of PD-1/PD-L1 Therapy Resistance in Breast Cancer.Cancer reports (Hoboken, N.J.) · 2025Article
- Calpains, the proteases of two faces controlling the epithelial homeostasis in mammary gland.Frontiers in cell and developmental biology · 2023Review
- Calpains as mechanistic drivers and therapeutic targets for ocular disease.Trends in molecular medicine · 2022Review
- Targeted inhibition of endothelial calpain delays wound healing by reducing inflammation and angiogenesis.Cell death & disease · 2020Article
- Proteomic analysis of Nrk gene-disrupted placental tissue cells explains physiological significance of NRK.BMC research notes · 2019Article
- Article
- High expression of Capn4 is associated with metastasis and poor prognosis in esophageal squamous cell carcinoma.International journal of clinical and experimental pathology · 2018Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
- Calpain-mediated Mechanoptosis in Breast Adenocarcinoma.Cancer diagnosis & prognosisReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Calpain is an intracellular Ca(2+)-regulated protease system whose substrates include proteins involved in proliferation, survival, migration, invasion, and sensitivity to therapeutic drugs. Genetic disruption of calpain attenuated the tumorigenic potential of breast cancer cells and hypersensitized cells to 17AAG, an inhibitor of the molecular chaperone HSP90. Calpain-1 or -2 overexpression rendered cells resistant to 17AAG, whereas downregulation or inhibition of calpain-1/2 led to increased cell death in multiple breast cancer cell lines, including models of HER2(+) (SKBR3) and triple-negative basal-cell-like (MDA-MB-231) breast cancer. In an MDA-MB-231 orthotopic xenograft model, calpain knockdown or 17AAG treatment independently attenuated tumor growth and metastasis, while the combination was most effective. Calpain knockdown was associated with increased 17AAG-induced degradation of the HSP90 clients cyclin D1 and AKT and multidrug resistance protein 2, which correlated with increased expression of antimitogenic p27(KIP1) and proapoptotic BIM proteins. Like other therapeutics, 17AAG can be effluxed by specific ABC transporters. Calpain expression positively correlated with the expression of P glycoprotein in mouse embryonic fibroblasts. Importantly, we show that calpain affects ABC transporter function and efflux of clinically relevant doxorubicin. These observations provide a compelling rationale for exploring the combination of calpain inhibition with new or existing cancer therapeutics.
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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.