ArticleThe Journal of biological chemistry2012
Calpain 2 regulates Akt-FoxO-p27(Kip1) protein signaling pathway in mammary carcinoma.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- The Piezo1-Ca2+-PI3k/Akt signaling axis as a context-dependent mechanotransduction node during skin wound healing.iScience · 2026Review
- Fedratinib treatment correlates with suppressed STAT3/AKT/calpain-1 signaling and inhibits hepatocellular carcinoma progression.Translational gastroenterology and hepatology · 2026Article
- The Urinary Proteome Differs with the Presence and Type of Breast Cancer.Journal of proteome research · 2025Article
- Subtype-specific divergent roles of calpain-1 and calpain-2 in basal A triple-negative breast cancer.BMC molecular and cell biology · 2025Article
- Article
- CAPN2 correlates with insulin resistance states in PCOS as evidenced by multi-dataset analysis.Journal of ovarian research · 2024Article
- Calpains, the proteases of two faces controlling the epithelial homeostasis in mammary gland.Frontiers in cell and developmental biology · 2023Review
- The role of calcium-calpain pathway in hyperthermia.Frontiers in molecular medicine · 2022Review
- Loss of p27Kip1 leads to expansion of CD4+ effector memory T cells and accelerates colitis-associated colon cancer in mice with a T cell lineage restricted deletion of Smad4.Oncoimmunology · 2020Article
- Pathogenesis of pediatric B-cell acute lymphoblastic leukemia: Molecular pathways and disease treatments.Oncology letters · 2020Review
- Article
- Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity.Archives of toxicology · 2019Article
- Calpain-2 Enhances Non-Small Cell Lung Cancer Progression and Chemoresistance to Paclitaxel via EGFR-pAKT Pathway.International journal of biological sciences · 2019Article
- Calpain 2 knockdown promotes cell apoptosis and restores gefitinib sensitivity through epidermal growth factor receptor/protein kinase B/survivin signaling.Oncology reports · 2018Article
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- Cytoplasmic FOXP1 expression is correlated with ER and calpain II expression and predicts a poor outcome in breast cancer.Diagnostic pathology · 2018Article
- Recurrent copy number alterations in young women with breast cancer.Oncotarget · 2018Article
- MicroRNA-132 protects hippocampal neurons against oxygen-glucose deprivation-induced apoptosis.International journal of immunopathology and pharmacology · 2017Article
- Article
- Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We investigated the role of the ubiquitously expressed calpain 2 isoform in breast tumor cell growth, migration, signaling, and tumorigenesis. RNAi-mediated knockdown of the capn2 transcript was used to manipulate expression of the catalytic subunit of calpain 2 in the AC2M2 mouse mammary carcinoma cell line. Stable knockdown of capn2 correlated with reduced in vitro proliferation rates, soft agar colony formation efficiency, and migration rates, indicating roles for calpain 2 in mitogenesis, survival, and motogenesis. Biochemical analysis showed increased levels of protein phosphatase 2A and reduced levels of activated Akt in calpain 2-deficient cells, and this correlated with increased levels of the FoxO3a target gene product p27(Kip1), a key regulator of cell proliferation. Calpain 2 deficiency in the AC2M2 cells correlated with enhanced nuclear localization of FoxO3a, consistent with it being in a derepressed state capable of regulating transcriptional targets. Orthotopically engrafted calpain 2 knockdown AC2M2 cells generated tumors with reduced growth rates and enhanced in vivo expression of p27(Kip1). In summary, calpain 2 deficiency correlated with reduced Akt activity, increased protein phosphatase 2A levels, derepression of FoxO3a, and enhanced expression of the p27(Kip1) tumor suppressor. These observations argue that calpain 2 promotes tumor cell growth both in vitro and in vivo through the PI3K-Akt-FoxO-p27(Kip1) signaling cascade. Inhibition of calpain 2 might therefore provide therapeutic benefits in the treatment of cancer.
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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.