ArticleThe Journal of biological chemistry2011
Inhibitors of Src and focal adhesion kinase promote endocrine specification: impact on the derivation of β-cells from human pluripotent stem cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 40 citations in OpenAlex.
- Improved Differentiation Towards Insulin Producing Beta-Cells Derived from Healthy Canine Pancreatic Ductal Organoids.Veterinary sciences · 2025Article
- Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.Cell communication and signaling : CCS · 2024Article
- Review
- Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation.Development (Cambridge, England) · 2022Article
- Enhanced differentiation of human pluripotent stem cells into pancreatic endocrine cells in 3D culture by inhibition of focal adhesion kinase.Stem cell research & therapy · 2020Article
- Extracellular Matrix-Associated Factors Play Critical Roles in Regulating Pancreatic β-Cell Proliferation and Survival.Endocrinology · 2019Review
- Article
- Integrin and FAK Regulation of Human Pluripotent Stem Cells.Current stem cell reports · 2017Review
- An inhibitor of fibroblast growth factor receptor-1 (FGFR1) promotes late-stage terminal differentiation from NGN3+ pancreatic endocrine progenitors.Scientific reports · 2016Article
- Engineering pancreatic tissues from stem cells towards therapy.Regenerative therapy · 2016Review
- Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs.Diabetes · 2013Article
- A small molecule inhibitor of SRC family kinases promotes simple epithelial differentiation of human pluripotent stem cells.PloS one · 2013Article
- Tissue engineering 2.0: guiding self-organization during pluripotent stem cell differentiation.Current opinion in biotechnology · 2012Review
- Is stage-specific embryonic antigen 4 a marker for human ductal stem/progenitor cells?BioResearch open access · 2012Article
- Nanog increases focal adhesion kinase (FAK) promoter activity and expression and directly binds to FAK protein to be phosphorylated.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stepwise approaches for the derivation of β-cells from human embryonic stem cells have been described. However, low levels of endocrine specification limit the final yield of insulin-producing β-cells. In this study, we show that the pyrrolo-pyrimidine Src family kinase (SFK) inhibitor PP2 effectively promotes the endocrine specification of human embryonic stem cell derivatives based on its capacity to induce the expression of proendocrine transcription factors (NGN3, NEUROD1, NKX2.2, and PAX4) and to significantly increase the final yield of insulin-positive cells. We further demonstrate that PP2 inhibits the activation of focal adhesion kinase (FAK), and selective inhibition of this kinase is also sufficient to induce early endocrine commitment based on increased expression of NGN3, NEUROD1, and NKX2.2. Additional studies using dominant negative constructs and isolated human fetal pancreata suggest that c-Src is at least partially responsible for inhibiting early endocrine specification. Mechanistically, we propose that inhibition of SFK/FAK signaling can promote endocrine specification by limiting activation of the TGFβR/Smad2/3 pathway. Moreover, we show that inhibition of SFK/FAK signaling suppresses cell growth, increases the expression of the β-cell-associated cyclin-dependent kinase inhibitor p57kip2, and simultaneously suppresses the expression of Id1 and Id2. This study has important implications for the derivation of β-cells for the cell-based therapy of diabetes and sheds new light on the signaling events that regulate early endocrine specification.
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