RAD23B mediated proteasomal degradation occurs through p38 MAPK/ATF-2/RAD23B axis under nutrient-deprived conditions in breast cancer

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International Pub Date : 2024-04-01 DOI:10.1002/cbin.12160

Sukumaran Sriaishwarya, Baddireddi Subhadra Lakshmi

{"title":"RAD23B mediated proteasomal degradation occurs through p38 MAPK/ATF-2/RAD23B axis under nutrient-deprived conditions in breast cancer","authors":"Sukumaran Sriaishwarya, Baddireddi Subhadra Lakshmi","doi":"10.1002/cbin.12160","DOIUrl":null,"url":null,"abstract":"<p>Metabolic reprogramming in cancer occurs due to interaction of cells with the surrounding tumor microenvironment. In the microenvironment of solid tumors, nutrient deprivation is induced by high consumption of nutrients and insufficient vasculature. Tumor cells alter their metabolic strategies to adapt to the microenvironment. To understand the role of these metabolic changes, in the current study, we have mimicked nutrient deprivation condition in vitro to evaluate the associated signaling pathways in breast cancer cells. In our study, we have shown that nutritional deprivation activated p38 MAPK and activating transcription factor-2 (ATF-2) by increased phosphorylation of Thr180/Tyr182 and Thr71, respectively, in breast cancer cells. Pharmacological inhibition of p38 MAPK showed increased cell viability and reduced expression of ATF-2 and RAD23B under nutrient starvation conditions. Further, silencing of ATF-2 showed increased cell viability and decreased expression of RAD23B under nutrient starvation conditions. This suggests the involvement of p38 MAPK/ATF-2/RAD23B axis as a signaling pathway under nutrition starvation in breast cancer cells. The RAD23B mediated proteasome activity was shown to be much higher under stress conditions indicating a crucial role of RAD23B as a target for breast cancer.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 7","pages":"973-983"},"PeriodicalIF":3.3000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12160","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Metabolic reprogramming in cancer occurs due to interaction of cells with the surrounding tumor microenvironment. In the microenvironment of solid tumors, nutrient deprivation is induced by high consumption of nutrients and insufficient vasculature. Tumor cells alter their metabolic strategies to adapt to the microenvironment. To understand the role of these metabolic changes, in the current study, we have mimicked nutrient deprivation condition in vitro to evaluate the associated signaling pathways in breast cancer cells. In our study, we have shown that nutritional deprivation activated p38 MAPK and activating transcription factor-2 (ATF-2) by increased phosphorylation of Thr180/Tyr182 and Thr71, respectively, in breast cancer cells. Pharmacological inhibition of p38 MAPK showed increased cell viability and reduced expression of ATF-2 and RAD23B under nutrient starvation conditions. Further, silencing of ATF-2 showed increased cell viability and decreased expression of RAD23B under nutrient starvation conditions. This suggests the involvement of p38 MAPK/ATF-2/RAD23B axis as a signaling pathway under nutrition starvation in breast cancer cells. The RAD23B mediated proteasome activity was shown to be much higher under stress conditions indicating a crucial role of RAD23B as a target for breast cancer.

查看原文本刊更多论文

在乳腺癌营养缺乏的条件下，RAD23B 通过 p38 MAPK/ATF-2/RAD23B 轴介导蛋白酶体降解。

癌症中的代谢重编程发生于细胞与周围肿瘤微环境的相互作用。在实体瘤的微环境中，营养物质的大量消耗和血管不足会导致营养匮乏。肿瘤细胞会改变其代谢策略以适应微环境。为了了解这些新陈代谢变化的作用，在本研究中，我们在体外模拟了营养匮乏条件，以评估乳腺癌细胞中的相关信号通路。我们的研究表明，营养缺乏通过增加乳腺癌细胞中 p38 MAPK 和激活转录因子-2（ATF-2）的 Thr180/Tyr182 和 Thr71 磷酸化激活了这两种信号通路。对 p38 MAPK 的药理抑制显示，在营养饥饿条件下，细胞活力增加，ATF-2 和 RAD23B 的表达减少。此外，在营养饥饿条件下，沉默 ATF-2 可提高细胞活力并降低 RAD23B 的表达。这表明，p38 MAPK/ATF-2/RAD23B 轴是乳腺癌细胞在营养饥饿条件下的信号通路。RAD23B 介导的蛋白酶体活性在应激条件下更高，这表明 RAD23B 作为乳腺癌靶点的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Biology International 生物-细胞生物学

CiteScore

7.60

自引率

0.00%

发文量

208

审稿时长

1 months

期刊介绍： Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.