The CDC42-interacting protein 4 controls epithelial cell cohesion and tumor dissemination.
The CDC42-interacting protein 4 controls epithelial cell cohesion and tumor dissemination.
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DOI：
10.1016/j.devcel.2014.08.006
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发表时间：
2014-09
影响因子：
11.8
通讯作者：
Y. Rolland;Paola Marighetti;C. Malinverno;S. Confalonieri;C. Luise;Nadia Ducano;A. Palamidessi;S. Bisi;H. Kajiho;Flavia Troglio;O. Shcherbakova;A. Dunn;A. Oldani;Letizia Lanzetti;P. P. Di Fiore-P.;Andrea Disanza;G. Scita
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文献类型：
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作者：
Y. Rolland;Paola Marighetti;C. Malinverno;S. Confalonieri;C. Luise;Nadia Ducano;A. Palamidessi;S. Bisi;H. Kajiho;Flavia Troglio;O. Shcherbakova;A. Dunn;A. Oldani;Letizia Lanzetti;P. P. Di Fiore-P.;Andrea Disanza;G. Scita
内吞蛋白的作用和上皮细胞粘附和肿瘤播散的分子机制还不清楚。在这里，我们报告说，内吞F-BAR的CDC 42相互作用蛋白4（CIP 4）所需的ERBB 2和TGF-β1诱导的细胞散射，乳腺癌（BC）细胞的运动和入侵到3D矩阵，并转化为乳腺导管原位癌浸润性癌在小鼠异种移植模型。CIP 4促进E-钙粘蛋白-CIP 4-SRC复合物的形成，该复合物控制SRC活化、E-钙粘蛋白内吞作用和肌球蛋白轻链激酶的局部磷酸化，从而影响产生切向力以破坏细胞-细胞连接所需的肌动球蛋白收缩性。CIP 4在ERBB 2阳性的人BC中上调，与增加的远处转移相关，并且是BC患者亚组中不良疾病结果的独立预测因子。因此，它关键地控制细胞-细胞凝聚力，并且是乳腺肿瘤中获得侵袭性表型所必需的。
The role of endocytic proteins and the molecular mechanisms underlying epithelial cell cohesion and tumor dissemination are not well understood. Here, we report that the endocytic F-BAR-containing CDC42-interacting protein 4 (CIP4) is required for ERBB2- and TGF-β1-induced cell scattering, breast cancer (BC) cell motility and invasion into 3D matrices, and conversion from ductal breast carcinoma in situ to invasive carcinoma in mouse xenograft models. CIP4 promotes the formation of an E-cadherin-CIP4-SRC complex that controls SRC activation, E-cadherin endocytosis, and localized phosphorylation of the myosin light chain kinase, thereby impinging on the actomyosin contractility required to generate tangential forces to break cell-cell junctions. CIP4 is upregulated in ERBB2-positive human BC, correlates with increased distant metastasis, and is an independent predictor of poor disease outcome in subsets of BC patients. Thus, it critically controls cell-cell cohesion and is required for the acquisition of an invasive phenotype in breast tumors.