14-3-3ζ Cooperates with ErbB2 to Promote Ductal Carcinoma In Situ Progression to Invasive Breast Cancer by Inducing Epithelial-Mesenchymal Transition

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• 作者：Jing Lu ; Hua Guo ; Warapen Treekitkarnmongkol ; Ping Li ; Jian Zhang ; Bin Shi ; Chen Ling ; Xiaoyan Zhou ; Tongzhen Chen ; Paul J. Chiao ; Xinhua Feng ; Victoria L. Seewaldt ; William J. Muller ; Aysegul Sahin ; Mien-Chie Hung ; Dihua Yu
• 刊名：Cancer Cell
• 出版年：2009
• 出版时间：8 September 2009
• 年：2009
• 卷：16
• 期：3
• 页码：195-207
• 全文大小：1766 K

文摘

Summary

ErbB2, a metastasis-promoting oncoprotein, is overexpressed in 25 % of invasive/metastatic breast cancers, but in 50 % –60 % of noninvasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3ζ in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3ζ overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3ζ overexpression reduced cell adhesion by activating the TGF-β/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition. Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3ζ had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.