Unraveling the Role of Adiponectin Receptors in Obesity-Related Breast Cancer

Abstract

Obesity has a noteworthy role in breast tumor initiation and progression. Among the mechanisms proposed, the most validated is the development of chronic low-grade inflammation, supported by immune cell infiltration along with dysfunction in adipose tissue biology, characterized by an imbalance in adipocytokines secretion and alteration of their receptors within the tumor microenvironment. Many of these receptors belong to the seven-transmembrane receptor family, which are involved in physiological features, such as immune responses and metabolism, as well as in the development and progression of several malignancies, including breast cancer. These receptors are classified as canonical (G protein-coupled receptors, GPCRs) and atypical receptors, which fail to interact and activate G proteins. Among the atypical receptors, adiponectin receptors (AdipoRs) mediate the effect of adiponectin, the most abundant adipocytes-derived hormone, on breast cancer cell proliferation, whose serum levels are reduced in obesity. The adiponectin/AdipoRs axis is becoming increasingly important regarding its role in breast tumorigenesis and as a therapeutic target for breast cancer treatment. The objectives of this review are as follows: to point out the structural and functional differences between GPCRs and AdipoRs, and to focus on the effect of AdipoRs activation in the development and progression of obesity-dependent breast cancer.

The Effectiveness of Metabolic Bariatric Surgery in Preventing Gynecologic Cancer - from Pathophysiology to Clinical Outcomes

“…The end results are multiple: cell proliferation (via cyclin D1), inhibition of apoptosis (via Bcl-2 family and surviving), increase of oncogenic signals (hypoxia-inducible factor-1 or HIF-1a, heat shock protein 90 or Hsp90), modifications of the extracellular matrix and facilitation of metastasis (via metalloproteases or MMPs and serpin), and angiogenesis (via vascular endothelial growth factor or VEGF) 32 . On the other hand, low levels of adiponectin lead to differential activation of its receptor via alternative signal transduction (induction of Ras-MAP kinase and mTOR pathways instead of activation of the PGC-1α pathway and inhibition of mTOR) 33 .…”

Exploring the multifaceted role of obesity in breast cancer progression

“…Adipocyte DNA methylation of the adiponectin promoter region is linked to decreased adiponectin levels in obesity. However, it has also been noted that AdipoR1 methylation is unaffected by obesity ( Naimo et al, 2023 ). Adiponectin was reported to exhibit anticancer properties (anti-proliferative, anti-migratory, and pro-apoptotic) ( Choi et al, 2018 ).…”

Role of Leptin and Adiponectin in Carcinogenesis

“…This adipokine, together with the n-6 or n-3 polyunsaturated fatty acids (PUFAs) produced by periprostatic adipose tissue in prostatic cancer, has anti-tumoral effects [69]. Lower expression of adiponectin, AdipoR2, leptin and ObRs in the breast TME might be indicators of more aggressive breast cancer phenotypes [65,70,71]. The interactions of adipokines with TME are summarized in Table 1.…”