New Study Elucidates Obesity’s Role in Fueling Breast Cancer Progression

Obesity and cancer are two major health challenges of our time, yet the link between them remains only partially understood. New research now highlights a molecular chain of events in estrogen receptor-positive breast cancer, revealing how leptin, a hormone produced by fat cells, signals cancer cells to grow. This leads to increased activity of the enzyme stearoyl-CoA desaturase (SCD), which fuels the growth and motility of cancer cells. The findings from a study in The American Journal of Pathology, published by Elsevier, provides insights into the obesity–breast cancer link and identifies potential new therapeutic targets to counter obesity-driven breast cancer progression.

According to the World Obesity Federation’s 2025 Atlas, the global number of adults living with obesity is projected to reach 1.13 billion by 2030. Given the well-established epidemiological link between obesity and breast cancer, elucidating the molecular mechanisms underlying this association has become a major research priority.

“By integrating transcriptomic, lipidomic, and functional analyses, we uncovered a crucial role of the leptin-SCD axis in breast cancer biology,” explains lead investigator of the study Ines Barone, PhD, of the University of Calabria, Italy. “Our data indicate that the combined upregulation of leptin and SCD identifies a subgroup of breast cancers with poorer recurrence-free survival. This metabolic signature could serve as a prognostic marker, helping to stratify patients according to obesity-related metabolic risk.”

The researchers found that blocking SCD activity abolished leptin-induced oncogenic traits, such as enhanced cell growth, motility, mitochondrial respiration, and adenosine triphosphate (ATP) molecule production. Together, these findings provide a mechanistic explanation for how obesity can fuel hormone-responsive breast cancer progression.

Dr. Barone concludes, “We were fascinated to see that selectively blocking SCD could almost completely counteract the pro-tumorigenic effects driven by leptin, revealing a striking vulnerability in this pathway. Our findings hold promise for patients with estrogen receptor-positive breast cancer, the most common subtype of breast cancer, as targeting SCD could limit disease progression in obese breast cancer patients.”

Notes for editors

The article is “Interplay between Leptin and Stearoyl-CoA Desaturase 1 in Estrogen Receptor—Positive Breast Cancer Cells,” by Felice Maria Accattatis, Luca Gelsomino, Linda Manna, Piercarlo Del Console, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Lorenzo Arnaboldi, Ludovica Baù, Alberto Corsini, Adele E. Leonetti, Rocco Malivindi, Marco Fiorillo, Michael P. Lisanti, Cinzia Giordano, Daniela Bonofiglio, Sebastiano Andò, Stefania Catalano, and Ines Barone (https://doi.org/10.1016/j.ajpath.2025.08.009). It appears in The American Journal of Pathology, volume 195, issue 12 (December 2025), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(25)00336-0/fulltext.

The authors would like to acknowledge that this work was the result of a true team effort involving multiple complementary skills from multiple universities: molecular biology (University of Calabria and University of Salford), lipidomics (University of Milan), and bioinformatics (University of Siena). Each group contributed to a different aspect of the study, and their combined efforts highlight both the interdisciplinary nature and the strength of this research.

This study was supported by the European Union’s NextGenerationEU initiative under the Italian Ministry of University and Research and by the Italian Association for Cancer Research (AIRC).

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected] to request a PDF of the article or more information. To reach the study’s authors, contact Stefania Catalano, MD, at [email protected] or Ines Barone, PhD, at [email protected].

About The American Journal of Pathology

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. ajp.amjpathol.org

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