Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, China.
Biomed Pharmacother. 2023 Jul;163:114762. doi: 10.1016/j.biopha.2023.114762. Epub 2023 Apr 24.
Autophagy helps maintain energy homeostasis and protect cells from stress effects by selectively removing misfolded/polyubiquitylated proteins, lipids, and damaged mitochondria. Cancer-associated fibroblasts (CAFs) are cellular components of tumor microenvironment (TME). Autophagy in CAFs inhibits tumor development in the early stages; however, it has a tumor-promoting effect in advanced stages. In this review, we aimed to summarize the modulators responsible for the induction of autophagy in CAFs, such as hypoxia, nutrient deprivation, mitochondrial stress, and endoplasmic reticulum stress. In addition, we aimed to present autophagy-related signaling pathways in CAFs, and role of autophagy in CAF activation, tumor progression, tumor immune microenvironment. Autophagy in CAFs may be an emerging target for tumor therapy. In summary, autophagy in CAFs is regulated by a variety of modulators and can reshape tumor immune microenvironment, affecting tumor progression and treatment.
自噬通过选择性去除错误折叠/多泛素化的蛋白质、脂质和受损的线粒体，有助于维持能量平衡并保护细胞免受应激效应的影响。癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）的细胞成分。CAFs 中的自噬在早期阶段抑制肿瘤的发展；然而，在晚期阶段，它具有促进肿瘤的作用。在这篇综述中，我们旨在总结负责诱导 CAFs 自噬的调节剂，如缺氧、营养剥夺、线粒体应激和内质网应激。此外，我们旨在介绍 CAFs 中的自噬相关信号通路，以及自噬在 CAF 激活、肿瘤进展、肿瘤免疫微环境中的作用。CAFs 中的自噬可能是肿瘤治疗的一个新靶点。总之，CAFs 中的自噬受多种调节剂的调控，并能重塑肿瘤免疫微环境，影响肿瘤的进展和治疗。
