了解癌症干细胞维持和耐药性的自噬功能
Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance
影响因子:5.50000
分区:医学3区 / 生化与分子生物学3区 医学：研究与实验3区
发表日期:2024 Oct 08
作者:
Niharika, Minal Garg
摘要
复杂的肿瘤生态系统包括肿瘤细胞及其相关的肿瘤微环境（TME）不断影响肿瘤行为，并最终影响治疗衰竭，疾病进展，复发和患者的总体存活率差。肿瘤细胞之间的串扰和TME之间通过创造代谢变化（例如缺氧环境和营养波动）来扩大复杂性。 TME的这些变化启动了癌细胞中的干细胞样程序，有助于肿瘤异质性并增加肿瘤鲁棒性。最近的研究表明，自噬在休眠期间长时间，转移性疾病的最终生长和抗病性的最终生长中，自噬在促进成纤维细胞产生，癌细胞存活中的多面作用。最近正在进行的研究将自噬/线粒体视为一种有力的生存策略，以应对环境压力，包括TME中的营养剥夺，缺氧和环境压力。它可以防止不可逆的衰老，促进类似茎状的状态，诱导上皮 - 间质转变，并增加肿瘤细胞的迁移和侵入性潜力。本综述讨论了癌细胞（CSC）表型自噬诱导诱导背后的各种理论和机制。鉴于自噬功能在CSC攻击性和治疗性抗性中的作用，讨论了基于抑制细胞可塑性的各种机制和研究，通过阻止自噬作为杀死肿瘤细胞的强大治疗策略。
Abstract
Complex tumour ecosystem comprising tumour cells and its associated tumour microenvironment (TME) constantly influence the tumoural behaviour and ultimately impact therapy failure, disease progression, recurrence and poor overall survival of patients. Crosstalk between tumour cells and TME amplifies the complexity by creating metabolic changes such as hypoxic environment and nutrient fluctuations. These changes in TME initiate stem cell-like programmes in cancer cells, contribute to tumoural heterogeneity and increase tumour robustness. Recent studies demonstrate the multifaceted role of autophagy in promoting fibroblast production, stemness, cancer cell survival during longer periods of dormancy, eventual growth of metastatic disease and disease resistance. Recent ongoing studies examine autophagy/mitophagy as a powerful survival strategy in response to environmental stress including nutrient deprivation, hypoxia and environmental stress in TME. It prevents irreversible senescence, promotes dormant stem-like state, induces epithelial-mesenchymal transition and increases migratory and invasive potential of tumour cells. The present review discusses various theories and mechanisms behind the autophagy-dependent induction of cancer stem cell (CSC) phenotype. Given the role of autophagic functions in CSC aggressiveness and therapeutic resistance, various mechanisms and studies based on suppressing cellular plasticity by blocking autophagy as a powerful therapeutic strategy to kill tumour cells are discussed.