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Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models
Tumor cells exploit multiple mechanisms to evade apoptosis, hence the strategies aimed at reactivating cell death in cancer. However, recent studies are revealing that dying cells play remarkable pro-oncogenic roles. Among the mechanisms promoting cell death, cell competition, elicited by disparitie...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871239/ https://www.ncbi.nlm.nih.gov/pubmed/36704198 http://dx.doi.org/10.3389/fcell.2022.1043630 |
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author | Sollazzo, Manuela Paglia, Simona Di Giacomo, Simone Grifoni, Daniela |
author_facet | Sollazzo, Manuela Paglia, Simona Di Giacomo, Simone Grifoni, Daniela |
author_sort | Sollazzo, Manuela |
collection | PubMed |
description | Tumor cells exploit multiple mechanisms to evade apoptosis, hence the strategies aimed at reactivating cell death in cancer. However, recent studies are revealing that dying cells play remarkable pro-oncogenic roles. Among the mechanisms promoting cell death, cell competition, elicited by disparities in MYC activity in confronting cells, plays the primary role of assuring tissue robustness during development from Drosophila to mammals: cells with high MYC levels (winners) overproliferate while killing suboptimal neighbors (losers), whose death is essential to process completion. This mechanism is coopted by tumor cells in cancer initiation, where host cells succumb to high-MYC-expressing precancerous neighbors. Also in this case, inhibition of cell death restrains aberrant cell competition and rescues tissue structure. Inhibition of apoptosis may thus emerge as a good strategy to counteract cancer progression in competitive contexts; of note, we recently found a positive correlation between cell death amount at the tumor/stroma interface and MYC levels in human cancers. Here we used Drosophila to investigate the functional role of competition-dependent apoptosis in advanced cancers, observing dramatic changes in mass dimensions and composition following a boost in cell competition, rescued by apoptosis inhibition. This suggests the role of competition-dependent apoptosis be not confined to the early stages of tumorigenesis. We also show that apoptosis inhibition, beside restricting cancer mass, is sufficient to rescue tissue architecture and counteract cell migration in various cancer contexts, suggesting that a strong activation of the apoptotic pathways intensifies cancer burden by affecting distinct phenotypic traits at different stages of the disease. |
format | Online Article Text |
id | pubmed-9871239 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98712392023-01-25 Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models Sollazzo, Manuela Paglia, Simona Di Giacomo, Simone Grifoni, Daniela Front Cell Dev Biol Cell and Developmental Biology Tumor cells exploit multiple mechanisms to evade apoptosis, hence the strategies aimed at reactivating cell death in cancer. However, recent studies are revealing that dying cells play remarkable pro-oncogenic roles. Among the mechanisms promoting cell death, cell competition, elicited by disparities in MYC activity in confronting cells, plays the primary role of assuring tissue robustness during development from Drosophila to mammals: cells with high MYC levels (winners) overproliferate while killing suboptimal neighbors (losers), whose death is essential to process completion. This mechanism is coopted by tumor cells in cancer initiation, where host cells succumb to high-MYC-expressing precancerous neighbors. Also in this case, inhibition of cell death restrains aberrant cell competition and rescues tissue structure. Inhibition of apoptosis may thus emerge as a good strategy to counteract cancer progression in competitive contexts; of note, we recently found a positive correlation between cell death amount at the tumor/stroma interface and MYC levels in human cancers. Here we used Drosophila to investigate the functional role of competition-dependent apoptosis in advanced cancers, observing dramatic changes in mass dimensions and composition following a boost in cell competition, rescued by apoptosis inhibition. This suggests the role of competition-dependent apoptosis be not confined to the early stages of tumorigenesis. We also show that apoptosis inhibition, beside restricting cancer mass, is sufficient to rescue tissue architecture and counteract cell migration in various cancer contexts, suggesting that a strong activation of the apoptotic pathways intensifies cancer burden by affecting distinct phenotypic traits at different stages of the disease. Frontiers Media S.A. 2023-01-10 /pmc/articles/PMC9871239/ /pubmed/36704198 http://dx.doi.org/10.3389/fcell.2022.1043630 Text en Copyright © 2023 Sollazzo, Paglia, Di Giacomo and Grifoni. 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 Sollazzo, Manuela Paglia, Simona Di Giacomo, Simone Grifoni, Daniela Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title | Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title_full | Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title_fullStr | Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title_full_unstemmed | Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title_short | Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models |
title_sort | apoptosis inhibition restrains primary malignant traits in different drosophila cancer models |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871239/ https://www.ncbi.nlm.nih.gov/pubmed/36704198 http://dx.doi.org/10.3389/fcell.2022.1043630 |
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