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EMP2作为黑色素瘤的抑制因子,受mTOR介导的自噬负调控。

EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.

作者信息

Wang Manyi, Li Sijia, Zhang Peng, Wang Yujia, Wang Chunting, Bai Ding, Jiang Xian

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, Department of Orthodontics and Paediatrics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.

Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu 610041, PR China.

出版信息

J Cancer. 2019 Jun 9;10(16):3582-3592. doi: 10.7150/jca.30342. eCollection 2019.

Abstract

Cutaneous melanoma is one of the most common malignant skin tumors and advanced melanoma is usually associated with a poor prognosis. In the current study, we demonstrated the tumor suppressing role of epithelial membrane protein-2 (EMP2) by inducing apoptosis in a A375 human melanoma cell line. Mechanistically, the low expression of EMP2 in melanoma is partially due to autophagic protein degradation mediated by the mTOR pathway. These results suggest there is regulation of autophagy as well as EMP2 levels might be an interesting novel targeted therapeutic strategy for melanoma. Although the further investigation is needed to deeply understand the regulatory mechanisms of EMP2 in melanoma progression and metastasis, our results clarify the functions and mechanisms of autophagy in melanoma, and shed new light on novel targeted therapeutics for melanoma.

摘要

皮肤黑色素瘤是最常见的恶性皮肤肿瘤之一,晚期黑色素瘤通常预后较差。在本研究中,我们通过诱导A375人黑色素瘤细胞系凋亡,证明了上皮膜蛋白2(EMP2)的肿瘤抑制作用。从机制上讲,黑色素瘤中EMP2的低表达部分归因于mTOR途径介导的自噬性蛋白质降解。这些结果表明,自噬调节以及EMP2水平可能是一种有趣的新型黑色素瘤靶向治疗策略。尽管需要进一步研究以深入了解EMP2在黑色素瘤进展和转移中的调控机制,但我们的结果阐明了自噬在黑色素瘤中的功能和机制,并为黑色素瘤的新型靶向治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d716/6636303/fcf8f122b1b9/jcav10p3582g001.jpg

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