کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151959 | 1090035 | 2009 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
MMPHNSCCHIF-1αICCFBSsiRNA - siRNAchromatin immunoprecipitation - ایمن سازی کروماتینImmunocytochemistry - ایمونوسیتوشیمیIHC - ایمونوهیستوشیمیImmunohistochemistry - ایمونوهیستوشیمیEMT - تکنسین فوریتهای پزشکیfetal bovine serum - سرم جنین گاوhypoxia-inducible factor-1 - فاکتور القای هیپوکسی -1matrix metalloproteinase - ماتریکس متالوپروتئینازCHiP - چیپHead and neck squamous cell carcinoma - کارسینوم سلول سنگفرشی سر و گردنEpithelial-mesenchymal transition - گذار اپیتلیال-مزانشیمی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 11, Issue 12, December 2009, Pages 1371-1382, IN12-IN14
Journal: Neoplasia - Volume 11, Issue 12, December 2009, Pages 1371-1382, IN12-IN14
نویسندگان
Chi-Hung Huang, Wen-Hao Yang, Shyue-Yih Chang, Shyh-Kuan Tai, Cheng-Hwei Tzeng, Jung-Yie Kao, Kou-Juey Wu, Muh-Hwa Yang,