14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition.

14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition.
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DOI:
10.1016/j.ccr.2009.08.010
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发表时间:
2009-09-08
期刊:
影响因子:
50.3
通讯作者:
Yu D
Yu D
中科院分区:
医学1区
文献类型:
--
作者:
Lu J;Guo H;Treekitkarnmongkol W;Li P;Zhang J;Shi B;Ling C;Zhou X;Chen T;Chiao PJ;Feng X;Seewaldt VL;Muller WJ;Sahin A;Hung MC;Yu D

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ErbB 2是一种促进转移的癌蛋白,在约25%的浸润性/转移性乳腺癌中过表达,但在50-60%的非浸润性导管原位癌(DCIS)中过表达。ErbB 2过表达的DCIS如何发展为浸润性乳腺癌(IBC)一直令人困惑。我们发现,在ErbB 2过表达的DCIS中,14-3-3 β的共过表达赋予了更高的进展为IBC的风险。ErbB 2和14-3-3过表达分别增加细胞迁移和降低细胞粘附,这是肿瘤细胞侵袭的两个先决条件。14-3-3 β过表达通过激活TGFβ/Smads途径降低细胞粘附,导致ZFHX 1B/SIP-1上调、E-钙粘蛋白丢失和上皮-间质转化(EMT)。重要的是,乳腺肿瘤同时过表达ErbB 2和14-3-3 β的患者比仅过表达其中一种的患者有更高的转移复发率和死亡率。
ErbB2, a metastasis-promoting oncoprotein, is overexpressed in ~25% of invasive/metastatic breast cancers, but in 50–60% of non-invasive 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 TGFβ/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition (EMT). 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.
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