Bustos Silvina Odete, Antunes Fernanda, Rangel Maria Cristina, Chammas Roger
Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina de São Paulo, Brazil.
Front Oncol. 2020 Nov 25;10:606436. doi: 10.3389/fonc.2020.606436. eCollection 2020.
The tumor microenvironment (TME) is a complex environment where cancer cells reside and interact with different types of cells, secreted factors, and the extracellular matrix. Additionally, TME is shaped by several processes, such as autophagy. Autophagy has emerged as a conserved intracellular degradation pathway for clearance of damaged organelles or aberrant proteins. With its central role, autophagy maintains the cellular homeostasis and orchestrates stress responses, playing opposite roles in tumorigenesis. During tumor development, autophagy also mediates autophagy-independent functions associated with several hallmarks of cancer, and therefore exerting several effects on tumor suppression and/or tumor promotion mechanisms. Beyond the concept of degradation, new different forms of autophagy have been described as modulators of cancer progression, such as secretory autophagy enabling intercellular communication in the TME by cargo release. In this context, the synthesis of senescence-associated secretory proteins by autophagy lead to a senescent phenotype. Besides disturbing tumor treatment responses, autophagy also participates in innate and adaptive immune signaling. Furthermore, recent studies have indicated intricate crosstalk between autophagy and the epithelial-mesenchymal transition (EMT), by which cancer cells obtain an invasive phenotype and metastatic potential. Thus, autophagy in the cancer context is far broader and complex than just a cell energy sensing mechanism. In this scenario, we will discuss the key roles of autophagy in the TME and surrounding cells, contributing to cancer development and progression/EMT. Finally, the potential intervention in autophagy processes as a strategy for cancer therapy will be addressed.
肿瘤微环境（TME）是一个复杂的环境，癌细胞在其中生存，并与不同类型的细胞、分泌因子和细胞外基质相互作用。此外，TME由多种过程塑造，如自噬。自噬已成为一种保守的细胞内降解途径，用于清除受损细胞器或异常蛋白质。凭借其核心作用，自噬维持细胞内稳态并协调应激反应，在肿瘤发生中发挥着相反的作用。在肿瘤发展过程中，自噬还介导与癌症的几个特征相关的非自噬依赖性功能，因此对肿瘤抑制和/或肿瘤促进机制产生多种影响。除了降解的概念外，新的不同形式的自噬已被描述为癌症进展的调节因子，如分泌性自噬通过货物释放实现TME中的细胞间通讯。在这种情况下，自噬合成衰老相关分泌蛋白会导致衰老表型。除了干扰肿瘤治疗反应外，自噬还参与先天性和适应性免疫信号传导。此外，最近的研究表明自噬与上皮-间质转化（EMT）之间存在复杂的相互作用，通过这种相互作用癌细胞获得侵袭性表型和转移潜力。因此，癌症背景下的自噬远比仅仅是一种细胞能量感知机制更为广泛和复杂。在这种情况下，我们将讨论自噬在TME和周围细胞中的关键作用，这些作用有助于癌症的发展和进展/EMT。最后，将探讨对自噬过程进行潜在干预作为癌症治疗策略的问题。
