Abstract
Epithelial cells acquire migratory/invasive and stemness traits upon conversion to the mesenchymal phenotype. The expression of E-cadherin is a key to this transition; yet precise understanding of the pathways involved in integrating E-cadherin loss to the gain of mesenchymal traits remains poorly understood. Here, we show that phosphoinositide-generating enzyme, PIPKIγ, expression is upregulated upon epithelial–mesenchymal transition (EMT) and together with the cytoskeletal protein talin assemble into a signaling complex upon E-cadherin loss. PIPKIγ and talin together control the adhesion and phosphoinositide signaling that regulates conversion to the mesenchymal phenotypes. PIPKIγ and talin regulate the stability of E-cadherin transcriptional repressors, snail and slug, induced by transforming growth factor-β1 or extracellular matrix protein. Loss of PIPKIγ or talin or their interaction impaired EMT and the acquisition of cell motility and stemness. This demonstrates a mechanism where a phosphoinositide-generating enzyme PIPKIγ couples with a cytoskeletal protein talin to control the acquisition of mesenchymal phenotypes.
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Acknowledgements
This work was supported by National Institute of Health (NIH) grants (CA104708 and GM057549) to RAA; American Heart Association (AHA) grants to NT (10POST4290052) and SC (13PRE14690057); and Howard Hughes Medical Institute (HHMI) International Student Research Fellowship to XT.
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Thapa, N., Tan, X., Choi, S. et al. PIPKIγ and talin couple phosphoinositide and adhesion signaling to control the epithelial to mesenchymal transition. Oncogene 36, 899–911 (2017). https://doi.org/10.1038/onc.2016.267
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DOI: https://doi.org/10.1038/onc.2016.267
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