ArticleThe Journal of clinical investigation2010
PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 97 citations in OpenAlex.
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- PINCH-1 promotes tumor growth and metastasis by enhancing DRP1-mediated mitochondrial fission in head and neck squamous cell carcinoma.Cancer biology & therapy · 2025Article
- Focus on Pancreatic Cancer Microenvironment.Current oncology (Toronto, Ont.) · 2024Review
- Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner.Scientific reports · 2022Article
- Growth factor receptor and β1 integrin signaling differentially regulate basal clonogenicity and radiation survival of fibroblasts via a modulation of cell cycling.In vitro cellular & developmental biology. Animal · 2022Article
- PINCH-1 promotes IGF-1 receptor expression and skin cancer progression through inhibition of the GRB10-NEDD4 complex.Theranostics · 2022Article
- Novel therapies targeting hypoxia mechanism to treat pancreatic cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2021Article
- Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states.Current stem cell reports · 2021Article
- MicroRNA-Dependent Targeting of RSU1 and the IPP Adhesion Complex Regulates the PTEN/PI3K/AKT Signaling Pathway in Breast Cancer Cell Lines.International journal of molecular sciences · 2020Article
- ATM-associated signalling triggers the unfolded protein response and cell death in response to stress.Communications biology · 2020Article
- The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner.Cancers · 2020Article
- Tumor Cell Invasion in Glioblastoma.International journal of molecular sciences · 2020Review
- PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis.Oncogene · 2020Article
- LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice.Bone research · 2020Article
- Article
- Review
- Rsu1-dependent control of PTEN expression is regulated via ATF2 and cJun.Journal of cell communication and signaling · 2019Article
- LIMS1 Promotes Pancreatic Cancer Cell Survival under Oxygen-Glucose Deprivation Conditions by Enhancing HIF1A Protein Translation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy.Frontiers in molecular biosciences · 2019Review
- Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells.International journal of oncology · 2018Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Tumor cell resistance to ionizing radiation and chemotherapy is a major obstacle in cancer therapy. One factor contributing to this is integrin-mediated adhesion to ECM. The adapter protein particularly interesting new cysteine-histidine-rich 1 (PINCH1) is recruited to integrin adhesion sites and promotes cell survival, but the mechanisms underlying this effect are not well understood. Here we have shown that PINCH1 is expressed at elevated levels in human tumors of diverse origins relative to normal tissue. Furthermore, PINCH1 promoted cell survival upon treatment with ionizing radiation in vitro and in vivo by perpetuating Akt1 phosphorylation and activity. Mechanistically, PINCH1 was found to directly bind to protein phosphatase 1alpha (PP1alpha) - an Akt1-regulating protein - and inhibit PP1alpha activity, resulting in increased Akt1 phosphorylation and enhanced radioresistance. Thus, our data suggest that targeting signaling molecules such as PINCH1 that function downstream of focal adhesions (the complexes that mediate tumor cell adhesion to ECM) may overcome radio- and chemoresistance, providing new therapeutic approaches for 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.