کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8308483 | 1538494 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HRD1-mediated PTEN degradation promotes cell proliferation and hepatocellular carcinoma progression
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed throughout the body and is involved in a variety of biological functions. PTEN is known to be frequently mutated or downregulated in human cancers. However, the underlying molecular mechanism remains largely unknown. Here, using a proteomic approach, we identified the E3 ubiquitin ligase HRD1, which was previously reported to be involved in endoplasmic reticulum associated degradation (ERAD), as one of the PTEN-interacting proteins. We also found that HRD1 promoted PTEN degradation by positively regulating its ubiquitination. In addition, suppression of HRD1 expression resulted in the inhibition of the growth, migration and invasion of hepatocellular carcinoma in vitro and in vivo. Finally, we detected a negative correlation between HRD1 and PTEN expression in human hepatocellular carcinoma. From these results we propose a novel molecular mechanism of HRD1 to promote hepatocellular tumorigenesis via PTEN inactivation. We conclude that targeting HRD1 may represent a new therapeutic strategy for PTEN-loss hepatocellular carcinoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 50, October 2018, Pages 90-99
Journal: Cellular Signalling - Volume 50, October 2018, Pages 90-99
نویسندگان
Liu Liu, Hua Long, Yan Wu, Hui Li, Ling Dong, Julia Li Zhong, Zhaojian Liu, Xiaolong Yang, Xiaotian Dai, Lei Shi, Maozhi Ren, Zhenghong Lin,