کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525424 1546668 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleN-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleN-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc
چکیده انگلیسی


- NDRG1 is overexpressed in NSCLC initiating cells.
- NDRG1 promotes stem-like properties of lung cancer cells.
- NDRG1 is negatively associated with lung cancer progression and prognosis.
- NDRG1 prevents the ubiquitylation of c-Myc by skp2.

Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC. NDRG1 prevented the degradation of c-Myc through Skp2-mediated ubiquitination. NDRG1 directly interacted with Skp2, and decreased phosphorylation of Skp2 through inactivation of CDK2. Finally, we confirmed that NDRG1 was negatively correlated with survival and prognosis. Thus, our findings indicate that NDRG1 is a potential target for eradicating TICs in NSCLC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 401, 10 August 2017, Pages 53-62
نویسندگان
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