Altered Lipolytic Protein Expression in Tumor-Associated Adipose Tissue Correlates with Aggressive Breast Cancer Features

Abstract

Background: Adipose tissue (AT) has emerged as a metabolically active component of the breast tumor microenvironment that contributes to breast cancer (BC) progression. Adipocytes release adipokines and lipids that influence tumor growth; however, the specific lipolytic proteins involved in these interactions remain poorly characterized. Methods: In this study, we analyzed the expression of perilipin 1, adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) by Western blot and immunofluorescence in adipose tissue explants from BC patients and healthy donors, evaluating their associations with clinicopathological features related to BC prognosis. Results: We found that perilipin 1 expression was increased in AT from patients with aggressive tumor characteristics, including advanced stage, premenopausal status, and obesity. In contrast, ATGL and HSL levels were reduced in specific patient subgroups, particularly in obese and postmenopausal patients and in tumor-adjacent AT from invasive lobular carcinoma. Conclusions: Together, these findings indicate that the expression of proteins involved in the regulation of lipolysis is influenced by both tumor proximity and clinicopathological characteristics, suggesting alterations in the molecular machinery governing lipid droplet regulation and lipid mobilization within tumor-associated AT. The observed associations identify perilipin 1, ATGL, and HSL as potential candidate markers of tumor-associated AT alterations and provide further insight into tumor–adipocyte interactions in BC. Despite the exploratory nature of this study, the observed associations provide a basis for further investigation into their potential biological and clinical relevance in BC.

The authors' abstract, as published at the source. Cancers, 2026 · DOI ↗