American Association for Cancer Research
Browse
00085472can082649-sup-can_1-15-09_arteaga.pdf (397.51 kB)

Supplementary Figure 1 from Transforming Growth Factor β Induces Clustering of HER2 and Integrins by Activating Src-Focal Adhesion Kinase and Receptor Association to the Cytoskeleton

Download (397.51 kB)
journal contribution
posted on 2023-03-30, 18:46 authored by Shizhen Emily Wang, Bin Xiang, Roy Zent, Vito Quaranta, Ambra Pozzi, Carlos L. Arteaga
Supplementary Figure 1 from Transforming Growth Factor β Induces Clustering of HER2 and Integrins by Activating Src-Focal Adhesion Kinase and Receptor Association to the Cytoskeleton

History

ARTICLE ABSTRACT

It has been proposed that cross talk between integrin and growth factor receptor signaling such as ErbB2 (HER2) is required for activation of downstream effectors and ErbB2-mediated mammary tumorigenesis. Here we show that transforming growth factor β (TGF-β) induced focal adhesion kinase (FAK)–dependent clustering of HER2 and integrins α6, β1, and β4 in HER2-overexpressing mammary epithelial cells without altering the total and surface levels of HER2 receptors. This effect was mediated by ligand-induced epidermal growth factor receptor (EGFR) activation and the subsequent phosphorylation of Src and FAK. We have previously reported that TGF-β up-regulates EGFR ligand shedding through a mechanism involving the phosphorylation of tumor necrosis factor-α–converting enzyme (TACE/ADAM17). Knockdown of TACE, FAK, or integrin α6 by siRNA or inhibition of EGFR or Src by specific inhibitors abrogated TGF-β–induced receptor clustering and signaling to phosphatidylinositol 3-kinase-Akt. Finally, inhibition of Src-FAK reversed TGF-β–induced resistance to the therapeutic HER2 inhibitor trastuzumab in HER2-overexpressing breast cancer cells. Taken together, these data suggest that, by activating Src-FAK, TGF-β integrates ErbB receptor and integrin signaling to induce cell migration and survival during breast cancer progression. [Cancer Res 2009;69(2):475–82]

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC