Role of Ambra 1 in the development and progression of squamous cell carcinomas

Abstract

Squamous cell carcinomas (SCC), also known as epidermoid carcinomas, comprise several different types of cancers that emerge from squamous cells. Cutaneous squamous cell carcinoma (cSCC) arising from malignant epidermal keratinocytes, is the second most frequent skin cancer in humans after basal cell carcinoma (BCC). This figure continues to rise and is underestimated. UV radiation is the main risk factor that generates a burden of mutations that trigger the development of cSCC. While it usually exhibits benign clinical behaviour, it can be locally invasive and metastatic. Ten-year survival after surgery exceeds 90% for cSCC but drops dramatically when metastases occur. Given its high frequency, cSCC has a significant impact on overall mortality. So, the identification of prognostic biomarkers would help identify the most aggressive tumours.The AMBRA1 protein, highly conserved among vertebrates, was discovered in 2007. Regarding protein structure, the intrinsic disorder accounts for the great plasticity, making AMBRA1 an excellent scaffold-molecular candidate able to interact with several proteins and thus, regulate a plethora of biological processes. In cancer, AMBRA1 has been identified as a tumour suppressor gene in the context of different types of neoplasms due to its ability to regulate proliferation and invasiveness...