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STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa
Arturo Valle-Mendiola1, Leticia Rocha-Zavaleta2, Vilma Maldonado-Lagunas3
1Laboratorio 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.
Abstract:
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 HIF1α 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.
Insights
Interleukin-2 (IL-2) promotes cervical cancer growth by altering cell metabolism via STAT5. Silencing STAT5 reversed these metabolic changes, highlighting its role in tumor energy demands.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Tumor cells reprogram metabolism to meet high energy demands for uncontrolled growth.
- Cytokines like Interleukin-2 (IL-2) activate signaling pathways, including JAK/STAT, influencing cellular processes.
- The JAK/STAT pathway's role in linking cytokine signaling to cancer cell metabolism is not fully understood.
Purpose of the Study:
- To investigate the effect of IL-2 on metabolic reprogramming in cervical cancer cells.
- To elucidate the specific role of STAT5 in IL-2-mediated metabolic changes and cell proliferation.
Main Methods:
- Analysis of IL-2's impact on cervical cancer cell proliferation and STAT5 phosphorylation.
- Measurement of lactate secretion and NAD+/NADH ratio to assess metabolic shifts.
- Gene expression analysis (HIF1α, GLUT1) following STAT5 silencing.
Main Results:
- IL-2 treatment increased cervical cancer cell proliferation, STAT5 phosphorylation, lactate secretion, and NAD+/NADH ratio.
- STAT5 silencing reduced lactate secretion, NAD+/NADH ratio, and expression of HIF1α and GLUT1.
- These findings indicate STAT5 mediates IL-2-induced aerobic glycolysis and cell proliferation.
Conclusions:
- STAT5 plays a crucial role in mediating IL-2-induced metabolic reprogramming in cervical cancer.
- STAT proteins regulate the metabolic switch to aerobic glycolysis, supporting cancer cell energy demands for growth and proliferation.
- Targeting the IL-2/STAT5 pathway could offer therapeutic strategies for cervical cancer.
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