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Updated: Aug 10, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGFβ instructs mTORC2 to activate PKCβII for increased TWIST1 expression in proximal tubular epithelial cell injury
Falguni Das1,2, Nandini Ghosh-Choudhury3, Soumya Maity2
11VA Research and 4Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, San Antonio, TX, 78229, USA.
Abstract:
The plasticity of proximal tubular epithelial cells in response to TGFβ contributes to the expression of TWIST1 to drive renal fibrosis. The mechanism of TWIST1 expression is not known. We show that both PI3 kinase and its target mTORC2 increase TGFβ-induced TWIST1 expression. TGFβ enhances phosphorylation on Ser-660 in the protein kinase C βII (PKCβII) hydrophobic motif site. Remarkably, phosphorylation-deficient PKCβIIS660A, kinase-dead PKCβII, and PKCβII knockdown blocked TWIST1 expression by TGFβ. Inhibition of TWIST1 arrested TGFβ-induced tubular cell hypertrophy and the expression of fibronectin, collagen I (α2), and α-smooth muscle actin. By contrast, TWIST1 overexpression induced these pathologies. Interestingly, the inhibition of PKCβII reduced these phenomena, which were countered by the expression of TWIST1. These results provide the first evidence for the involvement of the mTORC2-PKCβII axis in TWIST1 expression to promote tubular cell pathology.
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