Open Access

ARTICLE

GDF11 downregulates FOXP3 in T-cell acute lymphoblastic leukemia-derived cells and associates with restraining aggressiveness

MELISSA SáNCHEZ-RODRíGUEZ^1,2, ROBERTO LAZZARINI-LECHUGA³, VERóNICA SOUZA-ARROYO^1,4, LETICIA BUCIO-ORTIZ^1,4, ROXANA U. MIRANDA-LABRA^1,4, MONSERRAT GERARDO-RAMíREZ¹, ARACELI PáEZ-ARENAS⁵, MOISES VERGARA-MENDOZA⁶, MARíA CONCEPCIóN GUTIéRREZ-RUIZ^1,4, ALEJANDRO ESCOBEDO-CALVARIO^1,2,*, LUIS E. GOMEZ-QUIROZ^1,4,*

1 Área de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, 09340, Mexico
2 Posgrado en Biología Experimental. DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, 09340, Mexico
3 Departamento de Biología de la Reproducción, DCBS, Universidad Autónoma Metrolitana-Iztapalapa, Mexico City, 09340, Mexico
4 Laboratorio de Medicina Experimental, Unidad de Medicina Traslacional IIB/UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, 14080, Mexico
5 Laboratorio de Cardiología Traslacional, Unidad de Medicina Traslacional, IIB/UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, 14080, Mexico
6 Departamento de Enfermedades Infecciosas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico

* Corresponding Authors: ALEJANDRO ESCOBEDO-CALVARIO. Email: ; LUIS E. GOMEZ-QUIROZ. Email:

Oncology Research 2025, 33(8), 2075-2084. https://doi.org/10.32604/or.2025.064899

Received 26 February 2025; Accepted 22 May 2025; Issue published 18 July 2025

Abstract

Background: Growth differentiation factor 11 (GDF11), a transforming growth factor-beta superfamily member, is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis, and it has been extensively characterized due to its capacity to target poorly differentiated cells, including transformed or cancer cells. Aim: In the present work, we aimed to describe the effects on migration, proliferation, and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat. Methods: Based on previous evidence, we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype. Results: We found a profound impact on mitochondrial metabolism and reactive oxygen species content; these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3 (FOXP3), which is highly involved in aggressiveness in leukemia cells; this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment. Conclusion: The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.

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