Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Oral Biochemistry and Molecular Biology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2024 Aug 8;25(16):8647. doi: 10.3390/ijms25168647.
Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, as certain cancers tend to depend on autophagy for survival. Autophagy, while crucial for maintaining stemness in cancer stem cells (CSCs), can also serve as a vulnerability in certain contexts, making it a complex target for therapy. Regulators of autophagy like AMPK (5' adenosine monophosphate-activated protein kinase) also play a crucial role in maintaining CSCs stemness by helping CSCs in metabolic reprogramming in harsh environments. The purpose of this review is to elucidate the interplay between autophagy and AMPK in CSCs, highlighting the challenges in targeting autophagy and discussing therapeutic strategies to overcome these limitations. This review focuses on previous research on autophagy and its regulators in cancer biology, particularly in CSCs, addresses the remaining unanswered questions, and potential targets for therapy are also brought to attention.
肿瘤微环境中存在着一类具有自我更新、分化和抵抗化疗药物能力的肿瘤干细胞亚群，它们能够利用休眠作为保护机制。这些细胞具有独特的特性，包括耐药性和转移潜能，这给有效的靶向治疗带来了挑战。它们利用某些代谢过程来维持自身的生存和发展。其中一个过程是自噬，它通常有助于能量平衡，但当被肿瘤干细胞劫持时，它可以帮助维持其干细胞特性。因此，自噬通常被认为是肿瘤干细胞中的一个弱点，因为某些癌症往往依赖自噬来生存。自噬虽然对维持肿瘤干细胞的干性至关重要，但在某些情况下也可以作为一个弱点，使其成为治疗的一个复杂靶点。自噬的调节剂，如 AMPK（5' 腺苷单磷酸激活蛋白激酶），通过帮助肿瘤干细胞在恶劣环境中进行代谢重编程，在维持肿瘤干细胞干性方面也起着至关重要的作用。本综述的目的是阐明自噬和 AMPK 在肿瘤干细胞中的相互作用，强调了靶向自噬的挑战，并讨论了克服这些限制的治疗策略。本综述重点关注了自噬及其在癌症生物学中的调节剂的先前研究，特别是在肿瘤干细胞中，探讨了仍未解答的问题，并引起了对潜在治疗靶点的关注。
