Cell polarity is crucial for the correct structural and functional organization of epithelial tissue. Its disruption can lead to loss of the apicobasal polarity, alteration in the intracellular components, misregulation of the pathways involved in cell proliferation and
cancer promotion. Very recent in vitro/in vivo findings demonstrated that
obesity-associated alterations in tissue
adipokines protein level negatively affect epithelial polarity. We performed an in silico study to investigate whether such alterations also occur in surgical samples. We aimed to explore the relationship among the expression of the genes coding for
leptin (LEP),
adiponectin (ADIPOQ),
adipokine receptors (LEPR, ADIPOR1 and ADIPOR2), and a panel of polarity-associated genes in normal tissue from breast reduction
mammoplasty, and a series of paired samples of histologically normal (HN) tissue and invasive
cancer. Results indicated that, in normal tissue, the expression of
adipokines and their receptors negatively correlated with that of the polarity-associated genes and GGT1, which codes for γ-glutamyl
transferase (GGT)
enzyme, a marker of cell distress and membrane disruption. This negative correlation progressively decreased in HN and cancerous tissue, and loss of correlation between ADIPOR2 and polarity-associated genes appeared the most noticeable alteration. Given the growing role of
obesity in
breast cancer etiology and the opposite action of
leptin and
adiponectin in epithelial tissue remodeling, ADIPOR2 loss could be addressed as a key mechanism leading to an unbalanced
leptin stimulatory activity, subsequent cell polarity disruption and eventually
tumor initiation, a finding that requires to be confirmed also at the
protein level and with in vivo models.