POU1F1 transcription factor induces metabolic reprogramming and breast cancer progression via LDHA regulation
| العنوان: | POU1F1 transcription factor induces metabolic reprogramming and breast cancer progression via LDHA regulation |
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| المؤلفون: | Noemí Gómez-Lado, Manuel Macia, Efigenia Arias, Anxo Martinez-Ordoñez, Noemi Eiro, Tomás García-Caballero, Fabio Pereira, Samuel Seoane, Pablo Aguiar, Leandro Avila, Roman Perez-Fernandez, Francisco J. Vizoso |
| المساهمون: | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Universidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas, Universidade de Santiago de Compostela. Departamento de Fisioloxía |
| المصدر: | Oncogene Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lactate dehydrogenase A, Mice, Nude, Biology, Transfection, Article, Mice, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Immune system, Genetics, medicine, Animals, Humans, education, Molecular Biology, Transcription factor, Mice, Inbred BALB C, Gene knockdown, education.field_of_study, L-Lactate Dehydrogenase, Cancer, Cellular Reprogramming, medicine.disease, Mechanisms of disease, 030104 developmental biology, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Cancer cell, Disease Progression, MCF-7 Cells, Cancer research, Heterografts, Transcription Factor Pit-1 |
| الوصف: | Metabolic reprogramming is considered hallmarks of cancer. Aerobic glycolysis in tumors cells has been well-known for almost a century, but specific factors that regulate lactate generation and the effects of lactate in both cancer cells and stroma are not yet well understood. In the present study using breast cancer cell lines, human primary cultures of breast tumors, and immune deficient murine models, we demonstrate that the POU1F1 transcription factor is functionally and clinically related to both metabolic reprogramming in breast cancer cells and fibroblasts activation. Mechanistically, we demonstrate that POU1F1 transcriptionally regulates the lactate dehydrogenase A (LDHA) gene. LDHA catalyzes pyruvate into lactate instead of leading into the tricarboxylic acid cycle. Lactate increases breast cancer cell proliferation, migration, and invasion. In addition, it activates normal-associated fibroblasts (NAFs) into cancer-associated fibroblasts (CAFs). Conversely, LDHA knockdown in breast cancer cells that overexpress POU1F1 decreases tumor volume and [18F]FDG uptake in tumor xenografts of mice. Clinically, POU1F1 and LDHA expression correlate with relapse- and metastasis-free survival. Our data indicate that POU1F1 induces a metabolic reprogramming through LDHA regulation in human breast tumor cells, modifying the phenotype of both cancer cells and fibroblasts to promote cancer progression This study was supported by FEDER/Ministerio de Ciencia, Innovación y Universidades- Agencia Estatal de Investigación-PGC2018-100776-B-I00 and from Conselleria de Cultura, Educación e Ordenacion Universitaria (GPC2014/001), AM-O was supported by an FPU grant (Ministerio de Educación—FPU14/00548) SI |
| وصف الملف: | application/pdf |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a358d1462b424fffacaaaf3dad9744f0Test https://doi.org/10.1038/s41388-021-01740-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a358d1462b424fffacaaaf3dad9744f0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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