A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration
A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration
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DOI：
10.1038/ncb1622
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发表时间：
2007-08-01
影响因子：
21.3
通讯作者：
Yarden, Yosef
中科院分区：
文献类型：
--
作者：
Katz, Menachem;Amit, Ido;Yarden, Yosef
表皮生长因子受体（EGFR）驱动的细胞迁移促进形态发生（1），并涉及肌动蛋白细胞骨架的重组（2）。虽然从头转录先于迁移（3，4），但转录本身份在很大程度上仍然未知。通过肌动蛋白结合域，张力蛋白将细胞骨架连接到基于整合素的粘附位点（5）。在这里，我们报告说，EGF下调张力蛋白-3的表达，并伴随着上调cten，缺乏肌动蛋白结合域的张力蛋白家族成员（6）。cten或tensin-3的敲低分别损害或增强乳腺细胞迁移。此外，cten从整合素β（1）的胞质尾部置换张力蛋白-3，从而引发肌动蛋白纤维解体。在浸润性乳腺癌中，cten表达不仅与高EGFR和HER 2相关，而且与淋巴结转移相关。此外，用EGFR/HER 2双特异性激酶抑制剂治疗炎性乳腺癌患者显著下调cten表达。总之，转录张力蛋白-3-cten开关可能有助于乳腺癌的转移。
Cell migration driven by the epidermal growth factor receptor ( EGFR) propels morphogenesis(1) and involves reorganization of the actin cytoskeleton(2). Although de novo transcription precedes migration(3,4), transcript identity remains largely unknown. Through their actin-binding domains, tensins link the cytoskeleton to integrin-based adhesion sites(5). Here we report that EGF downregulates tensin-3 expression, and concomitantly upregulates cten, a tensin family member that lacks the actin-binding domain(6). Knockdown of cten or tensin-3, respectively, impairs or enhances mammary cell migration. Furthermore, cten displaces tensin-3 from the cytoplasmic tail of integrin beta(1), thereby instigating actin fibre disassembly. In invasive breast cancer, cten expression correlates not only with high EGFR and HER2, but also with metastasis to lymph nodes. Moreover, treatment of inflammatory breast cancer patients with an EGFR/HER2 dual-specificity kinase inhibitor significantly downregulated cten expression. In conclusion, a transcriptional tensin-3-cten switch may contribute to the metastasis of mammary cancer.