Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing; a complex process involving different dynamic events including migration of keratinocytes in the epidermis. Chronic wounds are estimated to affect 1–2% of the human population worldwide and are a major socioeconomic burden. The prevalence of chronic wounds is expected to increase with the rising number of elderly and patients with diabetes and obesity, who are at high risk of developing chronic wounds. Since E‐cadherin and the water channel aquaporin‐3 are important for both skin function and cell migration, and aquaporin‐3 is furthermore involved in wound healing of the skin demonstrated by impaired wound healing in aquaporin‐3‐null mice, we hypothesized that E‐cadherin and aquaporin‐3 expression may be dysregulated in chronic wounds. Therefore, we investigated the expression of E‐cadherin and aquaporin‐3 in biopsies from the edges of chronic wounds from human patients. This was accomplished by immunohistochemical stainings of E‐cadherin and aquaporin‐3 on serial sections followed by qualitative evaluation of staining patterns, which revealed low expression of both E‐cadherin and aquaporin‐3 at the wound edge. Future studies are needed to reveal if this downregulation is associated with the pathophysiology of chronic wounds.
Breast carcinomas originate from cells in the terminal duct-lobular unit. Carcinomas are associated with increased cell proliferation and migration, altered cellular adhesion, as well as loss of epithelial polarity. In breast cancer, aberrant and high levels of AQP5 are associated with increased metastasis, poor prognosis and cancer recurrence. AQP5 increases proliferation and migration of cancer cells, and ectopic expression of AQP5 in normal epithelial cells reduces cell-cell adhesion and increases cell detachment and dissemination from migrating cell sheets, the latter via AQP5 mediated activation of the Ras pathway. Here, we investigated if AQP5 also affects cellular polarity by examining the relationship between the essential polarity protein Scribble and AQP5. In tissue samples from invasive lobular and ductal carcinomas, the majority of cells with high AQP5 expression displayed low Scribble levels, indicating an inverse relationship. Probing for interactions via a GST pull-down experiment revealed that AQP5 and Scribble interacted. Moreover, overexpression of AQP5 in the breast cancer cell line MCF7 reduced both size and circularity of 3D spheroids and induced cell detachment and dissemination from migrating cell sheets. In addition, Scribble levels were reduced. An AQP5 mutant cell line, that cannot activate Ras (AQP5S156A), displayed unchanged spheroid size and circularity and an intermediate level of Scribble, indicating that the effect of AQP5 on Scribble is, at least in part, dependent of AQP5 mediated activation of Ras. Thus, our results suggest that high AQP5 expression negatively regulates the essential polarity protein Scribble and thus, can affect cellular polarity in breast cancer.
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