Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation.

IF 8.2 2区 生物学 Q1 CELL BIOLOGY Cell Communication and Signaling Pub Date : 2024-11-06 DOI:10.1186/s12964-024-01917-y
Ines Tawfik, Katharina Schlick, Julian Ostaku, Doruntina Bresilla, Sonja Gabrijelčič, Benjamin Gottschalk, Alwin Sokolowski, Ernst Malle, Katarina Kalinova, Martin Hirtl, Corina T Madreiter-Sokolowski
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Abstract

High levels of thyroid hormones are linked to increased risk and advanced stages of breast cancer. Our previous work demonstrated that the biologically active triiodothyronine (T3) facilitates mitochondrial ATP production by upregulating Ca2+ handling proteins, thereby boosting mitochondrial Ca2+ uptake and Krebs cycle activity. In this study, different cell types were utilized to investigate whether T3 activates a Ca2+-induced signaling pathway to boost cancer cell proliferation. Using live-cell imaging, biochemical assays, and molecular profiling, differences in intracellular signaling among MCF7 and MDA-MB-468 breast cancer cells, non-cancerous breast cells hTERT-HME1, and PC3 prostate carcinoma cells, previously found to be insensitive to thyroid hormones in terms of proliferation, were investigated. Our findings revealed that T3 upregulates 1,4,5-trisphosphate receptor 3 via thyroid hormone receptor α. This boosts mitochondrial Ca2+ uptake, reduction equivalent yield, and mitochondrial ATP production, supporting the viability and proliferation of breast cancer cells without affecting non-cancerous hTERT-HME1 or PC3 prostate carcinoma cells. Understanding the interplay between T3 signaling, organellar interaction, and breast cancer metabolism could lead to targeted therapies that exploit cancer cell vulnerabilities. Our findings highlight T3 as a crucial regulator of cancer metabolism, reinforcing its potential as a therapeutic target in breast cancer.

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乳腺癌细胞利用 T3 通过细胞 Ca2+ 调节引发增殖。
高水平的甲状腺激素与乳腺癌的风险增加和晚期阶段有关。我们之前的研究表明,具有生物活性的三碘甲状腺原氨酸(T3)通过上调 Ca2+ 处理蛋白促进线粒体 ATP 的产生,从而提高线粒体 Ca2+ 摄取和克雷布斯循环的活性。本研究利用不同类型的细胞来研究 T3 是否会激活 Ca2+ 诱导的信号通路,从而促进癌细胞增殖。通过活细胞成像、生化检测和分子谱分析,研究了MCF7和MDA-MB-468乳腺癌细胞、非癌乳腺细胞hTERT-HME1以及PC3前列腺癌细胞细胞内信号传导的差异。我们的研究结果表明,T3通过甲状腺激素受体α上调1,4,5-三磷酸受体3,从而促进线粒体Ca2+摄取、还原当量产量和线粒体ATP生成,支持乳腺癌细胞的活力和增殖,而不影响非癌细胞hTERT-HME1或PC3前列腺癌细胞。了解 T3 信号、细胞器相互作用和乳腺癌新陈代谢之间的相互作用,可以开发出利用癌细胞弱点的靶向疗法。我们的研究结果突显了 T3 是癌症代谢的关键调节因子,增强了其作为乳腺癌治疗靶点的潜力。
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来源期刊
CiteScore
11.00
自引率
0.00%
发文量
180
期刊介绍: Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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