Authors:
Jing Lu1, 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, and Dihua Yu
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.
Source:
Cancer Cell; Vol. 16, Issue 3, 195-207 (09/08/09)