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自噬在黑色素瘤演变中的复杂作用:来自小鼠模型的新视角

The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models.

作者信息

Di Leo Luca, Bodemeyer Valérie, De Zio Daniela

机构信息

Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark.

出版信息

Front Oncol. 2020 Jan 10;9:1506. doi: 10.3389/fonc.2019.01506. eCollection 2019.

Abstract

Despite tremendous efforts in the last decade to improve treatments, melanoma still represents a major therapeutic challenge and overall survival of patients remains poor. Therefore, identifying new targets to counteract melanoma is needed. In this scenario, autophagy, the "self-eating" process of the cell, has recently arisen as new potential candidate in melanoma. Alongside its role as a recycling mechanism for dysfunctional and damaged cell components, autophagy also clearly sits at a crossroad with metabolism, thereby orchestrating cell proliferation, bioenergetics and metabolic rewiring, all hallmarks of cancer cells. In this regard, autophagy, both in tumor and host, has been flagged as an essential player in melanomagenesis and progression. To pave the way to a better understanding of such a complex interplay, the use of genetically engineered mouse models (GEMMs), as well as syngeneic mouse models, has been undoubtedly crucial. Herein, we will explore the latest discoveries in the field, with particular focus on the potential of these models in unraveling the contribution of autophagy in melanoma, along with the therapeutic advantages that may arise.

摘要

尽管在过去十年中为改善治疗方法付出了巨大努力,但黑色素瘤仍然是一个重大的治疗挑战,患者的总体生存率仍然很低。因此,需要确定对抗黑色素瘤的新靶点。在这种情况下,自噬,即细胞的“自我吞噬”过程,最近已成为黑色素瘤新的潜在候选靶点。除了作为功能失调和受损细胞成分的循环机制外,自噬显然还处于与新陈代谢的交叉点,从而协调细胞增殖、生物能量学和代谢重塑,这些都是癌细胞的特征。在这方面,肿瘤和宿主中的自噬都被认为是黑色素瘤发生和进展的重要因素。为了更好地理解这种复杂的相互作用,使用基因工程小鼠模型(GEMMs)以及同基因小鼠模型无疑至关重要。在此,我们将探索该领域的最新发现,特别关注这些模型在揭示自噬在黑色素瘤中的作用以及可能产生的治疗优势方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7e4/6966767/1aa5f861418e/fonc-09-01506-g0001.jpg

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