ArticleThe Journal of biological chemistry2014
α6 integrin transactivates insulin-like growth factor receptor-1 (IGF-1R) to regulate caspase-3-mediated lens epithelial cell differentiation initiation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Ly6d expression delineates two putative postnatal thymus epithelial progenitor cells that are differentially affected by aging.Science advances · 2026Article
- Unveiling personalised targets of PD-1 blockade hyperprogression in a cervical adenocarcinoma via longitudinal single-cell and spatial monitoring.NPJ precision oncology · 2026Article
- Hypoxia-Driven Histone Modifications Govern Gene Regulation for Mature Eye Lens Formation.Investigative ophthalmology & visual science · 2025Article
- The link of FOXO1 and FOXO4 transcription factors to development of the lens.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer.EMBO molecular medicine · 2024Article
- Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.Science advances · 2024Article
- TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells.Journal of molecular histology · 2024Article
- Review
- Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone.Experimental cell research · 2022Article
- Mechanisms of organelle elimination for lens development and differentiation.Experimental eye research · 2021Review
- Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population.International journal of ophthalmology · 2020Article
- MicroRNA-744 promotes cell apoptosis via targeting B cell lymphoma-2 in gastric cancer cell line SGC-7901.Experimental and therapeutic medicine · 2018Article
- Molecular characterization of pro-metastatic functions of β4-integrin in colorectal cancer.Oncotarget · 2017Article
- Signaling and Gene Regulatory Networks in Mammalian Lens Development.Trends in genetics : TIG · 2017Review
- β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.Investigative ophthalmology & visual science · 2017Article
- Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens.Experimental and therapeutic medicine · 2016Article
- Surviving apoptosis: life-death signaling in single cells.Trends in cell biology · 2015Review
- Molecular characterization of mouse lens epithelial cell lines and their suitability to study RNA granules and cataract associated genes.Experimental eye research · 2015Article
- The cellular and molecular mechanisms of vertebrate lens development.Development (Cambridge, England) · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The canonical mitochondrial death pathway was first discovered for its role in signaling apoptosis. It has since been found to have a requisite function in differentiation initiation in many cell types including the lens through low level activation of the caspase-3 protease. The ability of this pathway to function as a molecular switch in lens differentiation depends on the concurrent induction of survival molecules in the Bcl-2 and IAP families, induced downstream of an IGF-1R/NFκB coordinate survival signal, to regulate caspase-3 activity. Here we investigated whether α6 integrin signals upstream to this IGF-1R-mediated survival-linked differentiation signal. Our findings show that IGF-1R is recruited to and activated specifically in α6 integrin receptor signaling complexes in the lens equatorial region, where lens epithelial cells initiate their differentiation program. In studies with both α6 integrin knock-out mice lenses and primary lens cell cultures following α6 integrin siRNA knockdown, we show that IGF-1R activation is dependent on α6 integrin and that this transactivation requires Src kinase activity. In addition, without α6 integrin, activation and expression of NFκB was diminished, and expression of Bcl-2 and IAP family members were down-regulated, resulting in high levels of caspase-3 activation. As a result, a number of hallmarks of lens differentiation failed to be induced; including nuclear translocation of Prox1 in the differentiation initiation zone and apoptosis was promoted. We conclude that α6 integrin is an essential upstream regulator of the IGF-1R survival pathway that regulates the activity level of caspase-3 for it to signal differentiation initiation of lens epithelial cells.
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Registered trials
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