Eva M Verdugo-Sivianes, Asunción Espinosa-Sánchez, Ildefonso Cases, Ana M Rojas, Daniel Otero-Albiol, Lourdes Romero, José Ramón Blanco, Amancio Carnero
{"title":"MEG8 as an antagonistic pleiotropic mechanism in breast cancer.","authors":"Eva M Verdugo-Sivianes, Asunción Espinosa-Sánchez, Ildefonso Cases, Ana M Rojas, Daniel Otero-Albiol, Lourdes Romero, José Ramón Blanco, Amancio Carnero","doi":"10.1038/s41420-024-02272-0","DOIUrl":null,"url":null,"abstract":"<p><p>Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes. Senescence itself constitutes a tumor suppression mechanism and plays a significant role in organismal aging by promoting chronic inflammation. Additionally, age is one of the major risk factors for developing breast cancer. Therefore, while senescence can suppress tumor development early in life, it can also lead to an aging process that drives the development of age-related pathologies, suggesting an antagonistic pleiotropic effect. In this work, we identified Rian/MEG8 as a potential biomarker connecting aging and breast cancer for the first time. We found that Rian/MEG8 expression decreases with age; however, it is high in mice that age prematurely. We also observed decreased MEG8 expression in breast tumors compared to normal tissue. Furthermore, MEG8 overexpression reduced the proliferative and stemness properties of breast cancer cells both in vitro and in vivo by activating apoptosis. MEG8 could exemplify the antagonistic pleiotropic theory, where senescence is beneficial early in life as a tumor suppression mechanism due to increased MEG8, resulting in fewer breast tumors at an early age. Conversely, this effect could be detrimental later in life due to aging and cancer, when MEG8 is reduced and loses its tumor-suppressive role.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"509"},"PeriodicalIF":6.1000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-024-02272-0","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes. Senescence itself constitutes a tumor suppression mechanism and plays a significant role in organismal aging by promoting chronic inflammation. Additionally, age is one of the major risk factors for developing breast cancer. Therefore, while senescence can suppress tumor development early in life, it can also lead to an aging process that drives the development of age-related pathologies, suggesting an antagonistic pleiotropic effect. In this work, we identified Rian/MEG8 as a potential biomarker connecting aging and breast cancer for the first time. We found that Rian/MEG8 expression decreases with age; however, it is high in mice that age prematurely. We also observed decreased MEG8 expression in breast tumors compared to normal tissue. Furthermore, MEG8 overexpression reduced the proliferative and stemness properties of breast cancer cells both in vitro and in vivo by activating apoptosis. MEG8 could exemplify the antagonistic pleiotropic theory, where senescence is beneficial early in life as a tumor suppression mechanism due to increased MEG8, resulting in fewer breast tumors at an early age. Conversely, this effect could be detrimental later in life due to aging and cancer, when MEG8 is reduced and loses its tumor-suppressive role.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.