静脉注射
癌症研究
转移
罗亚
转化生长因子
上皮-间质转换
乳腺癌
信号转导
CDC42型
信号转导衔接蛋白
埃兹林
焦点粘着
生物
癌症
细胞生物学
医学
内科学
细胞
细胞骨架
遗传学
作者
Yi He,Marie-Anne Goyette,Jennifer Chapelle,Nadia Boufaied,Jalal Al Rahbani,Maribel Schonewolff,Eric I. Danek,William J. Muller,David P. Labbé,Jean‐François Côté,Nathalie Lamarche-Vane
出处
期刊:Cell Reports
[Elsevier]
日期:2023-08-01
卷期号:42 (8): 112936-112936
被引量:1
标识
DOI:10.1016/j.celrep.2023.112936
摘要
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.
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