STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa
Por:
Valle-Mendiola A., Rocha-Zavaleta L., Maldonado-Lagunas V., Morelos-Laguna D., Gutiérrez-Hoya A., Weiss-Steider B., Soto-Cruz I.
Publicada:
1 ene 2024
Resumen:
The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1a and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation. © 2024 by the authors.
Filiaciones:
Valle-Mendiola A.:
Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, FES Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Col. Ejército de Oriente, Mexico City, 09230, Mexico
Rocha-Zavaleta L.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Maldonado-Lagunas V.:
Laboratorio de Epigenética, Instituto Nacional de Medicina Genómica (INMEGEN), Periférico Sur no. 4809, Col. Arenal Tepepan, Tlalpan, Mexico City, 14610, Mexico
Morelos-Laguna D.:
Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, FES Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Col. Ejército de Oriente, Mexico City, 09230, Mexico
Gutiérrez-Hoya A.:
Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, FES Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Col. Ejército de Oriente, Mexico City, 09230, Mexico
Cátedra CONAHCYT, FES Zaragoza, Universidad Nacional Autónoma de México, Mexico City, 68020, Mexico
Weiss-Steider B.:
Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, FES Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Col. Ejército de Oriente, Mexico City, 09230, Mexico
Soto-Cruz I.:
Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, FES Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de Mayo s/n Col. Ejército de Oriente, Mexico City, 09230, Mexico
gold, All Open Access; Gold Open Access
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