How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer.
How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer.
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DOI：
10.3389/fonc.2020.599915
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发表时间：
2020
影响因子：
4.7
通讯作者：
Isidoro C
中科院分区：
文献类型：
--
作者：
Ferraresi A;Girone C;Esposito A;Vidoni C;Vallino L;Secomandi E;Dhanasekaran DN;Isidoro C
卵巢癌（Ovarian cancer，OC）的特点是由于诊断晚和转移潜能高而导致死亡率高。自噬是一种溶酶体驱动的分解代谢过程，有助于大分子周转、细胞稳态和存活，因此，它代表了抗癌治疗的靶向途径。现在认识到，肿瘤微环境的血管形成和细胞组成通过控制营养物质、氧气、生长因子以及炎症和免疫调节可溶性因子的可用性来影响OC的发展和进展，这些可溶性因子最终影响癌细胞中的自噬调节。越来越多的证据表明，OC致癌作用与自噬不足有关，至少在早期阶段是这样。另一方面，当肿瘤已经建立时，自噬激活为面临代谢应激的癌细胞提供了生存优势，并保护其免受化疗和放疗引起的大分子和细胞器损伤。此外，自噬的上调可能导致癌细胞进入非增殖性休眠状态，保护细胞免受毒性损伤，同时保持其干细胞样特性。使情况进一步复杂化的是，自噬在基质细胞中也被失调。因此，肿瘤微环境的变化反映了癌症和基质细胞之间的代谢串扰，影响其自噬水平，从而影响癌症进展。在这里，我们简要概述了自噬在OC标志中的作用，包括肿瘤休眠，化疗耐药性，转移和细胞代谢，重点是癌细胞和基质细胞之间的双向代谢串扰，塑造OC微环境。
Ovarian cancer (OC) is characterized by a high mortality rate due to the late diagnosis and the elevated metastatic potential. Autophagy, a lysosomal-driven catabolic process, contributes to the macromolecular turnover, cell homeostasis, and survival, and as such, it represents a pathway targetable for anti-cancer therapies. It is now recognized that the vascularization and the cellular composition of the tumor microenvironment influence the development and progression of OC by controlling the availability of nutrients, oxygen, growth factors, and inflammatory and immune-regulatory soluble factors that ultimately impinge on autophagy regulation in cancer cells. An increasing body of evidence indicates that OC carcinogenesis is associated, at least in the early stages, to insufficient autophagy. On the other hand, when the tumor is already established, autophagy activation provides a survival advantage to the cancer cells that face metabolic stress and protects from the macromolecules and organelles damages induced by chemo- and radiotherapy. Additionally, upregulation of autophagy may lead cancer cells to a non-proliferative dormant state that protects the cells from toxic injuries while preserving their stem-like properties. Further to complicate the picture, autophagy is deregulated also in stromal cells. Thus, changes in the tumor microenvironment reflect on the metabolic crosstalk between cancer and stromal cells impacting on their autophagy levels and, consequently, on cancer progression. Here, we present a brief overview of the role of autophagy in OC hallmarks, including tumor dormancy, chemoresistance, metastasis, and cell metabolism, with an emphasis on the bidirectional metabolic crosstalk between cancer cells and stromal cells in shaping the OC microenvironment.
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DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
11.2
作者：
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影响因子：
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作者：
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