| First Author | He Y | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 112936 |
| PubMed ID | 37552602 | Mgi Jnum | J:339924 |
| Mgi Id | MGI:7525081 | Doi | 10.1016/j.celrep.2023.112936 |
| Citation | He Y, et al. (2023) CdGAP is a talin-binding protein and a target of TGF-beta signaling that promotes HER2-positive breast cancer growth and metastasis. Cell Rep 42(8):112936 |
| abstractText | 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 beta (TGF-beta)-induced EMT transcriptional signature. CdGAP is positively regulated by TGF-beta 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-beta-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-beta and integrin/talin signaling pathways. |
