Metabolic rewiring at the obesity-estrogen-polyamine axis in endometrial cancer: emerging mechanisms and translational opportunities.
5 affiliations
- 1Center for Evidence Ecosystems, Implementation Science, and Decision-Making (CIDES), Facultad de Ciencias de la Salud y Bienestar Humano, Universidad Tecnológica Indoamérica, Ambato, Ecuador.
- 2Escuela de Medicina, Universidad Espíritu Santo, Samborondón, Ecuador.
- 3School of Allied Health, Eastwick College, Ramsey, NJ, United States.
- 4Carrera de Laboratorio Clínico, Facultad de Ciencias Médicas, Universidad de Cuenca, Cuenca, Ecuador.
- 5Grupo de Investigación en Salud Sexual y Reproductiva, Departamento de Investigación en Salud Pública, Universidad de Cuenca, Cuenca, Ecuador.
Abstract
Endometrial cancer is one of the gynecologic malignancies most strongly associated with obesity, yet the biological basis of this association extends beyond excess adiposity as a risk factor. Obesity reshapes the endometrial ecosystem through peripheral estrogen excess, progesterone imbalance, insulin resistance, adipokine dysregulation, chronic inflammation, and activation of anabolic signaling pathways. These mechanisms converge on metabolic programs that support proliferation, invasion, immune remodeling, and treatment resistance. Polyamine metabolism is emerging as a potentially relevant but still incompletely validated layer of this biology. Ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, is overexpressed in aggressive endometrial cancers and has been associated with recurrence and poor survival. Recent evidence further suggests that metabolic syndrome-associated oleic acid may stabilize homeobox B9, protect ornithine decarboxylase 1 from degradation, increase polyamine accumulation, and promote tumor progression. This Mini Review critically examines the obesity-estrogen-polyamine axis as an integrative framework linking endocrine dysfunction, inflammatory remodeling, lipid signaling, and proliferative metabolic rewiring in endometrial cancer. It also discusses biomarker opportunities, therapeutic vulnerabilities, and the translational gaps that must be addressed before this axis can inform precision oncology.
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BibTeX
@article{simancasracines2026metabolic,
title = {{Metabolic rewiring at the obesity-estrogen-polyamine axis in endometrial cancer: emerging mechanisms and translational opportunities.}},
author = {Daniel Simancas-Racines and Dolores Jima Gavilanes and Andri Matos and Gabriele Davide Bigoni-Ordóñez and Claudia Reytor-González},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1954981},
url = {https://europepmc.org/article/MED/42922976},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metabolic rewiring at the obesity-estrogen-polyamine axis in endometrial cancer: emerging mechanisms and translational opportunities.
AU - Daniel Simancas-Racines
AU - Dolores Jima Gavilanes
AU - Andri Matos
AU - Gabriele Davide Bigoni-Ordóñez
AU - Claudia Reytor-González
PY - 2026
DA - 2026/10/08
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1954981
UR - https://europepmc.org/article/MED/42922976
AB - Endometrial cancer is one of the gynecologic malignancies most strongly associated with obesity, yet the biological basis of this association extends beyond excess adiposity as a risk factor. Obesity reshapes the endometrial ecosystem through peripheral estrogen excess, progesterone imbalance, insulin resistance, adipokine dysregulation, chronic inflammation, and activation of anabolic signaling pathways. These mechanisms converge on metabolic programs that support proliferation, invasion, immune remodeling, and treatment resistance. Polyamine metabolism is emerging as a potentially relevant but still incompletely validated layer of this biology. Ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, is overexpressed in aggressive endometrial cancers and has been associated with recurrence and poor survival. Recent evidence further suggests that metabolic syndrome-associated oleic acid may stabilize homeobox B9, protect ornithine decarboxylase 1 from degradation, increase polyamine accumulation, and promote tumor progression. This Mini Review critically examines the obesity-estrogen-polyamine axis as an integrative framework linking endocrine dysfunction, inflammatory remodeling, lipid signaling, and proliferative metabolic rewiring in endometrial cancer. It also discusses biomarker opportunities, therapeutic vulnerabilities, and the translational gaps that must be addressed before this axis can inform precision oncology.
SN - 2296-634X
ER -