| Autor: |
He, Yi, Goyette, Marie-Anne, Chapelle, Jennifer, Boufaied, Nadia, Al Rahbani, Jalal, Schonewolff, Maribel, Danek, Eric I., Muller, William J., Labbé, David P., Côté, Jean-François, Lamarche-Vane, Nathalie |
| Zdroj: |
Cell Reports; Aug2023, Vol. 42 Issue 8, pN.PAG-N.PAG, 1p |
| Abstrakt: |
Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. Here, we show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2+) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites. CdGAP depletion in HER2+ murine primary tumors mediates crosstalk with a Dlc1-RhoA pathway and is associated with a transforming growth factor β (TGF-β)-induced EMT transcriptional signature. CdGAP is positively regulated by TGF-β signaling during EMT and interacts with the adaptor talin to modulate focal adhesion dynamics and integrin activation. Moreover, HER2+ breast cancer patients with high CdGAP mRNA expression combined with a high TGF-β-EMT signature are more likely to present lymph node invasion. Our results suggest CdGAP as a candidate therapeutic target for HER2+ metastatic breast cancer by inhibiting TGF-β and integrin/talin signaling pathways. [Display omitted] • CdGAP promotes HER2-driven breast tumor progression and lung metastasis • CdGAP mediates crosstalk with a Dlc1-RhoA axis in HER2+ breast tumors • CdGAP interacts with talin to modulate integrin activation in HER2+ breast cancer • In humans, high CdGAP with a TGF-β-EMT signature is linked to disease progression The epithelial-to-mesenchymal transition (EMT) process is critical during tumor cell dissemination and propagation to distant organs. He et al. show that CdGAP is a key modulator of a TGF-β-induced EMT gene signature in HER2+ breast tumors, which contributes to tumor progression and lung metastasis in HER2-driven breast cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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