Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation
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 mitochondria...
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BMC
2024-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01917-y |
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| author | Ines Tawfik Katharina Schlick Julian Ostaku Doruntina Bresilla Sonja Gabrijelčič Benjamin Gottschalk Alwin Sokolowski Ernst Malle Katarina Kalinova Martin Hirtl Corina T. Madreiter-Sokolowski |
| author_facet | Ines Tawfik Katharina Schlick Julian Ostaku Doruntina Bresilla Sonja Gabrijelčič Benjamin Gottschalk Alwin Sokolowski Ernst Malle Katarina Kalinova Martin Hirtl Corina T. Madreiter-Sokolowski |
| author_sort | Ines Tawfik |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| format | Article |
| id | doaj-art-b3df8364ac434bdf84e6ec940e14d621 |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-b3df8364ac434bdf84e6ec940e14d6212025-08-20T02:50:08ZengBMCCell Communication and Signaling1478-811X2024-11-0122111810.1186/s12964-024-01917-yBreast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulationInes Tawfik0Katharina Schlick1Julian Ostaku2Doruntina Bresilla3Sonja Gabrijelčič4Benjamin Gottschalk5Alwin Sokolowski6Ernst Malle7Katarina Kalinova8Martin Hirtl9Corina T. Madreiter-Sokolowski10Division of Molecular Biology and Biochemistry, Medical University of GrazDepartment of Medicine I, Division of Oncology, Medical University of ViennaDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Restorative Dentistry, Periodontology and Prosthodontics, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazDivision of Molecular Biology and Biochemistry, Medical University of GrazAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12964-024-01917-yThyroid hormonesCalcium homeostasisBreast cancerIP3R3MitochondriaThyroid hormone receptor α |
| spellingShingle | Ines Tawfik Katharina Schlick Julian Ostaku Doruntina Bresilla Sonja Gabrijelčič Benjamin Gottschalk Alwin Sokolowski Ernst Malle Katarina Kalinova Martin Hirtl Corina T. Madreiter-Sokolowski Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation Cell Communication and Signaling Thyroid hormones Calcium homeostasis Breast cancer IP3R3 Mitochondria Thyroid hormone receptor α |
| title | Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation |
| title_full | Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation |
| title_fullStr | Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation |
| title_full_unstemmed | Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation |
| title_short | Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation |
| title_sort | breast cancer cells utilize t3 to trigger proliferation through cellular ca2 modulation |
| topic | Thyroid hormones Calcium homeostasis Breast cancer IP3R3 Mitochondria Thyroid hormone receptor α |
| url | https://doi.org/10.1186/s12964-024-01917-y |
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