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Cell Density Sensing Alters TGF-β Signaling in a Cell-Type-Specific Manner, Independent from Hippo Pathway Activation

Abstract : Cell-cell contacts inhibit cell growth and proliferation in part by activating the Hippo pathway that drives the phosphorylation and nuclear exclusion of the transcriptional coactivators YAP and TAZ. Cell density and Hippo signaling have also been reported to block transforming growth factor β (TGF-β) responses, based on the ability of phospho-YAP/TAZ to sequester TGF-β-activated SMAD complexes in the cytoplasm. Herein, we provide evidence that epithelial cell polarization interferes with TGF-β signaling well upstream and independent of cytoplasmic YAP/TAZ. Rather, polarized basolateral presentation of TGF-β receptors I and II deprives apically delivered TGF-β of access to its receptors. Basolateral ligand delivery nonetheless remains entirely effective to induce TGF-β responses. These data demonstrate that cell-type-specific inhibition of TGF-β signaling by cell density is restricted to polarized epithelial cells and reflects the polarized distribution of TGF-β receptors, which thus affects SMAD activation irrespective of Hippo pathway activation.
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https://www.hal.inserm.fr/inserm-03165090
Contributor : Mauviel Alain <>
Submitted on : Wednesday, March 10, 2021 - 1:36:28 PM
Last modification on : Thursday, March 11, 2021 - 3:36:10 AM

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Flore Nallet-Staub, Xueqian Yin, Cristele Gilbert, Véronique Marsaud, Saber Ben mimoun, et al.. Cell Density Sensing Alters TGF-β Signaling in a Cell-Type-Specific Manner, Independent from Hippo Pathway Activation. Developmental Cell, Elsevier, 2015, 32 (5), pp.640-651. ⟨10.1016/j.devcel.2015.01.011⟩. ⟨inserm-03165090⟩

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