ArticleFrontiers in oncology2022
Integrin α6β4 signals through DNA damage response pathway to sensitize breast cancer cells to cisplatin.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Gemcitabine-induced β4 integrin drives cancer progression and gemcitabine resistance in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- ST3GAL1 drives colorectal cancer metastasis by mediating NRF2-induced activation of the integrin-α6β4 signaling pathway via sialylation modification.Journal of translational medicine · 2026Article
- Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial-Mesenchymal Transition.Cancers · 2025Review
- Article
- Integrins as the pivotal regulators of cisplatin response in tumor cells.Cell communication and signaling : CCS · 2024Review
- Microsatellite instability states serve as predictive biomarkers for tumors chemotherapy sensitivity.iScience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Integrin α6β4 is highly expressed in triple negative breast cancer (TNBC) and drives its most aggressive traits; however, its impact on chemotherapeutic efficacy remains untested. We found that integrin α6β4 signaling promoted sensitivity to cisplatin and carboplatin but not to other chemotherapies tested. Mechanistic investigations revealed that integrin α6β4 stimulated the activation of ATM, p53, and 53BP1, which required the integrin β4 signaling domain. Genetic manipulation of gene expression demonstrated that mutant p53 cooperated with integrin α6β4 for cisplatin sensitivity and was necessary for downstream phosphorylation of 53BP1 and enhanced ATM activation. Additionally, we found that in response to cisplatin-induced DNA double strand break (DSB), integrin α6β4 suppressed the homologous recombination (HR) activity and enhanced non-homologous end joining (NHEJ) repair activity. Finally, we discovered that integrin α6β4 preferentially activated DNA-PK, facilitated DNA-PK-p53 and p53-53BP1 complex formation in response to cisplatin and required DNA-PK to enhance ATM, 53BP1 and p53 activation as well as cisplatin sensitivity. In summary, we discovered a novel function of integrin α6β4 in promoting cisplatin sensitivity in TNBC through DNA damage response pathway.
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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.