Cutaneous Squamous Cell Carcinoma (cSCC) represents about 20% of all non-melanoma skin cancers, with a dramatic increase in incidence in immunosuppressed patients. Since metastases of this disease are associated with a poor prognosis, there is interest in identifying new biomarkers of SCC metastasis as this could indicate new therapeutic targets. One potential candidate is the serine/threonine kinase AKT. AKT exists in two isoforms in the skin- AKT1 and AKT2- which perform different functions during skin homeostasis. AKT1 is important in the formation of the skin barrier, while AKT2 has been associated with wound healing and tumorigenesis. In this study we explored expression changes of the AKT isoforms in cSCC, utilising both a series of cSCC cell lines, as well as staining tissue sections from disease patients. We observed a marked increase in phosphorylation (activation) of AKT corresponding with tumour progression across the cSCC cell lines. Tissue staining revealed the levels of phospho-AKT2 to be elevated in tumours. Meanwhile, in immunosuppressed and poorly differentiated malignancies, AKT1 activity appeared to decline. Therefore, it seems that loss of AKT1 and gain of AKT2 may be drivers in cSCC, especially in poorly differentiated and immunosuppressed cases. Based on these data, future efforts will be geared towards identifying different substrates of the two AKT isoforms in cSCC, with the goal of finding novel druggable targets to prevent tumour progression.

Understanding the roles of AKT1 loss and AKT2 activation during SCC progression