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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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Autores principales: Fukuda, Tomohiko, Wada-Hiraike, Osamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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