Zaarour Rania F, Azakir Bilal, Hajam Edries Y, Nawafleh Husam, Zeinelabdin Nagwa A, Engelsen Agnete S T, Thiery Jérome, Jamora Colin, Chouaib Salem
Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman 4184, UAE.
Faculty of Medicine, Beirut Arab University, Beirut, Lebanon.
Cancers (Basel). 2021 Jan 30;13(3):533. doi: 10.3390/cancers13030533.
Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.
程序性细胞死亡或I型凋亡已得到广泛研究,其在疾病发病机制中的作用也已得到充分证实。然而,自噬与凋亡共同作用以决定细胞的整体命运。这种主动自我破坏过程与凋亡之间的相互作用相当复杂且矛盾,但对于细胞存活或死亡无疑具有决定性作用。自噬既能通过诱导癌细胞发展和增殖促进肿瘤抑制,也能促进肿瘤生长。在本综述中,我们将讨论在肿瘤缺氧应激背景下自噬如何重编程肿瘤细胞。我们将说明自噬如何通过以依赖于环境的方式调节存活,既是肿瘤发生的抑制因子又是驱动因子。我们还将阐明在这种复杂调节中自噬与免疫反应之间的关系。更好地理解自噬机制和途径无疑将改善旨在靶向自噬用于未来癌症免疫治疗的疗法设计。