کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151595 | 1090006 | 2012 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Integrin-Associated CD151 Drives ErbB2-Evoked Mammary Tumor Onset and Metastasis
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کلمات کلیدی
conventional PKCtetraspanin-enriched microdomainERBB2FAKERKEGFRPKCcPKCMMTVImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیTem - این استMouse mammary tumor virus - ویروس تومور پستان موشProtein kinase C - پروتئین کیناز سیextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیfocal adhesion kinase - کیناز چسبندگی کانونیEstrogen receptor - گیرنده استروژنEpidermal growth factor receptor 2 - گیرنده عامل فاکتور رشد اپیدرمال 2Epidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
ErbB2+ human breast cancer is a major clinical problem. Prior results have suggested that tetraspanin CD151 might contribute to ErbB2-driven breast cancer growth, survival, and metastasis. In other cancer types, CD151 sometimes supports tumor growth and metastasis. However, a definitive test of CD151 effects on de novo breast cancer initiation, growth, and metastasis has not previously been done. We used CD151 gene-deleted mice expressing the MMTV-ErbB2 transgene to show that CD151 strongly supports ErbB2+ mammary tumor initiation and metastasis. Delayed tumor onset (by 70-100 days) in the absence of CD151 was accompanied by reduced survival of mammary epithelial cells and impaired activation of FAK- and MAPK-dependent pathways. Both primary tumors and metastatic nodules showed smooth, regular borders, consistent with a less invasive phenotype. Furthermore, consistent with impaired oncogenesis and decreased metastasis, CD151-targeted MCF-10A/ErbB2 cells showed substantial decreases in three-dimensional colony formation, EGF-stimulated tumor cell motility, invasion, and transendothelial migration. These CD151-dependent functions were largely mediated through α6β4 integrin. Moreover, CD151 ablation substantially prevented PKC- and EGFR/ERK-dependent α6β4 integrin phosphorylation, consistent with retention of epithelial cell polarity and intermediate filament cytoskeletal connections, which helps to explain diminished metastasis. Finally, clinical data analyses revealed a strong correlation between CD151 and ErbB2 expression and metastasis-free survival of breast cancer patients. In conclusion, we provide strong evidence that CD151 collaborates with LB integrins (particularly α6β4) and ErbB2 (and EGFR) receptors to regulate multiple signaling pathways, thereby driving mammary tumor onset, survival, and metastasis. Consequently, CD151 is a useful therapeutic target in malignant ErbB2+ breast cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 8, August 2012, Pages 678-689, IN2-IN3
Journal: Neoplasia - Volume 14, Issue 8, August 2012, Pages 678-689, IN2-IN3
نویسندگان
Xinyu Deng, Qinglin Li, John Hoff, Marian Novak, Helen Yang, Hongyan Jin, Sonia F. Erfani, Chandan Sharma, Pengcheng Zhou, Isaac Rabinovitz, Arnoud Sonnenberg, Yajun Yi, Peter Zhou, Christopher S. Stipp, David M. Kaetzel, Martin E. Hemler,