Expressed in high metastatic cells (Ehm2) is a positive regulator of keratinocyte adhesion and motility: The implication for wound healing

Background: Multiple factors have been shown to delay dermal wound healing. These resultant wounds pose a significant problem in terms of morbidity and healthcare spend. Recently, an increasing volume of research has focused on the molecular perturbations underlying non-healing wounds.

Objectives: This study investigates the effect of a novel Cancer promoter, Ehm2, in wound healing. Ehm2 belongs to the FERM family of proteins, known to be involved in membrane-cytoskeletal interactions, and has been shown to promote Cancer metastasis in melanoma, prostate Cancer and breast Cancer.

Methods: Ehm2 mRNA levels were analysed using qRT-PCR, standardised to GAPDH, from either acute or chronic wounds, and normal skin. IHC analysis was also undertaken from wound edge biopsies. An anti-Ehm2 transgene was created and transfected into the HaCaT cell line. The effect of Ehm2 knockdown on migration, adhesion, growth, cell cycle progression and Apoptosis was analysed using standard laboratory methods. Western Blot analysis was used to investigate potential downstream protein interactions.

Results: Ehm2 is expressed nearly three times higher in acute wound tissues, compared to chronic wound tissues. Increased Ehm2 expression is found in wounds undergoing healing, especially at the leading wound edge. In vitro, Ehm2 knockdown reduces cellular adhesion, migration and motility, without affecting growth, cell cycle and Apoptosis. Finally, Ehm2 knockdown results in reduced NWasp protein expression.

Conclusion: These results suggest Ehm2 may be an important player in the wound healing process, and show that Ehm2 knockdown downregulates the expression of NWasp, through which it may have its effect on cellular migration.

ECIS; Ehm2; HaCaT; Keratinocytes; Wound healing.