Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
Nat Commun. 2017 Mar 16;8:14797. doi: 10.1038/ncomms14797.
The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.
衔接蛋白 p140Cap 负向调控肿瘤细胞特征。但其对乳腺癌患者生存的相关性，以及其对相关癌症信号通路的拮抗能力，尚未完全阐明。本研究报道，在 ERBB2 扩增型乳腺癌患者中，p140Cap 阳性状态与发生远处转移事件的概率显著降低以及生存差异明确相关。p140Cap 抑制 ERBB2 阳性肿瘤细胞的进展，在 NeuT 小鼠模型中削弱肿瘤起始和生长，并抑制上皮间质转化，从而减少转移形成。其主要机制之一是 p140Cap 干扰 ERBB2 依赖性 Rac GTPase 调控通路的激活。本研究结果表明，p140Cap 在抑制 ERBB2 扩增型乳腺癌的侵袭性方面具有特定作用，并提示由于其能够影响特定的分子通路，p140Cap 可能成为预测对靶向抗 ERBB2 治疗反应的生物标志物。
