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Updated: Apr 19, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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aPKC alters the TGFβ response in NSCLC cells through both Smad-dependent and Smad-independent pathways

Adrian Gunaratne, Eddie Chan, Tarek H El-Chabib

    Journal of Cell Science
    |December 16, 2014
    PubMed

    Insights

    aPKC inhibition reduces TGFb-dependent gene expression in NSCLC cells by disrupting Smad nuclear translocation. This leads to increased apoptosis via p38 MAPK and TRAF6 signaling, suggesting aPKC as a therapeutic target.

    Area of Science:

    • Cellular Biology
    • Molecular Signaling
    • Cancer Research

    Background:

    • Transforming growth factor beta (TGFb) signaling is crucial for cellular functions, involving both canonical (Smad) and non-canonical pathways.
    • Previous research indicated that atypical protein kinase C (aPKC) inhibition affects TGFb receptor trafficking and signaling.

    Purpose of the Study:

    • To investigate the role of aPKC in regulating TGFb signaling pathways in non-small cell lung cancer (NSCLC).
    • To elucidate how aPKC silencing impacts TGFb-dependent transcriptional responses and apoptosis in NSCLC cells.

    Main Methods:

    • Silencing of aPKC in NSCLC cells.
    • Assessment of TGFb-dependent transcriptional responses.
    • Analysis of Smad2 phosphorylation, SARA–Smad2–Smad4 association, and Smad2 nuclear translocation.
    • Evaluation of p38 MAPK phosphorylation and apoptosis, including TRAF6 dependency.

    Main Results:

    • aPKC silencing reduced TGFb-dependent gene expression despite prolonged Smad2 phosphorylation.
    • Knockdown of aPKC increased SARA levels and SARA–Smad2 complex formation, impairing Smad2–Smad4 association and nuclear translocation.
    • Increased p38 MAPK phosphorylation and apoptosis were observed in aPKC-silenced cells, dependent on TRAF6.

    Conclusions:

    • aPKC isoforms regulate both Smad and non-Smad TGFb signaling pathways.
    • Inhibition of aPKC sensitizes NSCLC cells to TGFb-induced apoptosis, highlighting a potential therapeutic strategy.

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