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PEAK1 Acts as a Molecular Switch to Regulate Context-Dependent TGFβ Responses in Breast Cancer

Fig 8

PEAK1 regulates TGFβ switching between tumor suppressor and pro-metastatic functions in breast cancer.

PEAK1 can bind and facilitate the recruitment of Src kinase to integrins and TβRII/Grb2 complexes to facilitate non-canonical TGFβ-induced MAPK signaling in the presence of extracellular matrix proteins that signal through ITGB3. Additionally, PEAK1 can promote Smad2/3 in the presence of fibronectin while potentiating TGFβ-induced Smad2/3 signaling in the absence of ECM protein. Ultimately, PEAK1 converts TGFβ signaling from an anti-proliferative growth factor to a pro-tumorigenic one.

Fig 8

doi: https://doi.org/10.1371/journal.pone.0135748.g008