Department of Biochemistry, All India Institute of Medical Science, Patna 801507, India.
Department of Molecular Medicine & Biotechnology, Sanjay Gandhi Post Graduate Institute of Medical Science, Lucknow 226014, India.
Cells. 2024 Mar 4;13(5):447. doi: 10.3390/cells13050447.
Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.
肿瘤由失调细胞的异质群体组成，这些细胞在专门的小生境中生长，这些小生境支持它们的生长并维持其特性。肿瘤异质性和转移是治疗癌症患者时存在的主要障碍之一，导致临床结局不佳。尽管决定肿瘤复杂性的因素在很大程度上仍然未知，但包括 DNA 突变和代谢重编程在内的几种基因型和表型变化为癌细胞提供了相对于宿主细胞的生存优势，并对治疗产生抗性。此外，肿瘤块内存在特定的细胞群体，通常称为癌症干细胞 (CSC)，被认为是肿瘤形成、维持、抵抗和复发的起点。因此，这些 CSCs 最近已被详细研究，作为治疗癌症和预防复发的潜在靶点。了解 CSC 增殖、自我更新和休眠中涉及的分子机制可能为开发有效的治疗策略提供重要线索。自噬是一种分解代谢过程，长期以来一直被认为可以调节各种生理和病理过程。除了调节癌细胞外，最近的研究还确定了自噬在调节 CSC 功能中的关键作用。自噬在各种不利条件下被激活，并促进细胞维持、存活甚至细胞死亡。因此，令人感兴趣的是要确定自噬是促进还是抑制 CSC 功能，以及自噬调节是否可以单独或联合用于调节 CSC 功能。这篇综述描述了自噬在调节 CSC 的代谢功能、增殖和静止中的作用，以及自噬在治疗压力下的作用。该综述进一步强调了可以用于调节 CSCs 的自噬相关途径。总体而言，本综述将有助于合理利用各种涉及自噬介导的 CSCs 调节的转化方法来控制癌症进展、转移和复发。
