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The Two-Faced Role of Autophagy in Endometrial Cancer
Autophagy, meaning “self-eating,” is a cellular catabolic process that involves lysosomal degradation of cytoplasmic materials. Autophagy contributes to both quality control and energy supply of cells, which are associated with tumorigenesis and tumor development, respectively. Endometrial cancer (E...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008213/ https://www.ncbi.nlm.nih.gov/pubmed/35433698 http://dx.doi.org/10.3389/fcell.2022.839416 |
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author | Fukuda, Tomohiko Wada-Hiraike, Osamu |
author_facet | Fukuda, Tomohiko Wada-Hiraike, Osamu |
author_sort | Fukuda, Tomohiko |
collection | PubMed |
description | Autophagy, meaning “self-eating,” is a cellular catabolic process that involves lysosomal degradation of cytoplasmic materials. Autophagy contributes to both quality control and energy supply of cells, which are associated with tumorigenesis and tumor development, respectively. Endometrial cancer (EC) is the most common gynecologic cancer, and its incidence is increasing. Although autophagy plays crucial roles in several types of cancer, such as pancreatic ductal adenocarcinoma, its role in EC has not been clearly demonstrated. Activation of the PI3K/AKT/mTOR pathway, which functions to suppress autophagy, is an initial step in type 1 endometrial carcinogenesis, whereas a loss-of-function mutation of TP53, which augments autophagy via p16 induction, is the main cause of type 2 endometrial carcinogenesis. Mutations in autophagy-related genes, including ATG4C, RB1CC1/FIP200, and ULK4, have been reported in EC; thus, an aberrant autophagy mechanism may be involved in endometrial carcinogenesis. Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC. These findings suggest that autophagy negatively regulates endometrial carcinogenesis, and autophagy inducers may be useful for chemoprevention of EC. In contrast, autophagy appears to promote EC once it is established. Consistent with this, treatment with chloroquine, an autophagy inhibitor, is reported to attenuate EC cell proliferation. Moreover, chemotherapy-induced autophagy triggers chemoresistance in EC cells. As autophagy has a tumor-promoting function, the combination of chemotherapy and autophagy inhibitors such as chloroquine could be a potent therapeutic option for patients with EC. In conclusion, autophagy plays a dual role in the prevention and treatment of EC. Therefore, targeting autophagy to prevent and treat EC requires diametrically opposed strategies. |
format | Online Article Text |
id | pubmed-9008213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90082132022-04-15 The Two-Faced Role of Autophagy in Endometrial Cancer Fukuda, Tomohiko Wada-Hiraike, Osamu Front Cell Dev Biol Cell and Developmental Biology Autophagy, meaning “self-eating,” is a cellular catabolic process that involves lysosomal degradation of cytoplasmic materials. Autophagy contributes to both quality control and energy supply of cells, which are associated with tumorigenesis and tumor development, respectively. Endometrial cancer (EC) is the most common gynecologic cancer, and its incidence is increasing. Although autophagy plays crucial roles in several types of cancer, such as pancreatic ductal adenocarcinoma, its role in EC has not been clearly demonstrated. Activation of the PI3K/AKT/mTOR pathway, which functions to suppress autophagy, is an initial step in type 1 endometrial carcinogenesis, whereas a loss-of-function mutation of TP53, which augments autophagy via p16 induction, is the main cause of type 2 endometrial carcinogenesis. Mutations in autophagy-related genes, including ATG4C, RB1CC1/FIP200, and ULK4, have been reported in EC; thus, an aberrant autophagy mechanism may be involved in endometrial carcinogenesis. Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC. These findings suggest that autophagy negatively regulates endometrial carcinogenesis, and autophagy inducers may be useful for chemoprevention of EC. In contrast, autophagy appears to promote EC once it is established. Consistent with this, treatment with chloroquine, an autophagy inhibitor, is reported to attenuate EC cell proliferation. Moreover, chemotherapy-induced autophagy triggers chemoresistance in EC cells. As autophagy has a tumor-promoting function, the combination of chemotherapy and autophagy inhibitors such as chloroquine could be a potent therapeutic option for patients with EC. In conclusion, autophagy plays a dual role in the prevention and treatment of EC. Therefore, targeting autophagy to prevent and treat EC requires diametrically opposed strategies. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9008213/ /pubmed/35433698 http://dx.doi.org/10.3389/fcell.2022.839416 Text en Copyright © 2022 Fukuda and Wada-Hiraike. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Fukuda, Tomohiko Wada-Hiraike, Osamu The Two-Faced Role of Autophagy in Endometrial Cancer |
title | The Two-Faced Role of Autophagy in Endometrial Cancer |
title_full | The Two-Faced Role of Autophagy in Endometrial Cancer |
title_fullStr | The Two-Faced Role of Autophagy in Endometrial Cancer |
title_full_unstemmed | The Two-Faced Role of Autophagy in Endometrial Cancer |
title_short | The Two-Faced Role of Autophagy in Endometrial Cancer |
title_sort | two-faced role of autophagy in endometrial cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008213/ https://www.ncbi.nlm.nih.gov/pubmed/35433698 http://dx.doi.org/10.3389/fcell.2022.839416 |
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