**Acknowledgements**

Another important role in carcinogenesis is attributed to cancer stem cells which derive from the transformation of normal cell or through the differentiation of tumor cells migrating through normal tissue. CD 133 is one of the most important biomarkers linked to proliferation and differentiation of skin cancers so that new therapeutic targets are needed to be focused on

Regarding the molecular aspects of cutaneous SCC, studies have shown not only the high levels of complement factor H and factor H-like protein 1 mRNA in comparison with normal skin, but also stronger expression in SCC than *in situ* carcinoma or actinic keratosis. In addition, it was demonstrated that knocking down CFH and FHL-1 lead to the inhibition of proliferation and migrations of SCC cells, suggesting their importance as progression markers and

An important aspect in risk evaluation for SCC is the integrity of immune systems. The high incidence of this malignancy in patients with compromised immune system was observed, pointing out the role of HLA system which varies between immunocompetent and immuno-

Other biomarkers involved in SCC development and progression are MMPs, serine peptidase and their inhibitors (Serpin-A1 being associated with tumorigenic change of keratinocytes and tumor progression). The metastatic prediction is attributed to EGFR and nuclear active IκB kinase (IKK) expression, thus a promising cSCC therapy is represented by EGFR inhibitors. Oral squamous cell carcinoma is associated with EGFR that not only activates the proteintyrosine kinase system involved in cell multiplication and differentiation, but also plays an important role in OSCC resilience to radiotherapy. Others biomarkers associated with OSCC are p53/p63 and Bcl-2. Tumor invasion is correlated with both matrix degradation enzymes

Genital squamous cell carcinoma is linked with p16 (in less aggressive form of vulvar SCC), p53 (weaker prognosis), cofilin-1, galectin-7 and weel. HPV infection plays an important role in SCC induction and evolution through the deactivation of tumor suppression genes by E6

Overall, skin cell carcinoma is one of the most frequent malignancy worldwide that even if it is easily treated and the cure rate is high, there are cases when metastasize can occur. An accurate clinical exam correlated with histological, immunohistochemical and proteomic investigation can establish the biomarkers involved in the development and evolution of this

Due to the fact that SCC is associated with frequent recurrence and sometimes metastasis, it is necessary to realize the study of biological transformation that occurs in these types of cancers. The discovery of various biomarkers can outline the occurrence, evolution and the

It is important to focus on the analysis of normal, inflammatory and malignant keratinocyte proteome in order to determine novel biomarkers that are associated with the development and progression of SCC and therefore can be used in the early detection, risk assessment,

and E7. Increased Hsp70 is also increased in this type of cancer.

prognosis of this keratinocyte-derived tumor.

malignancy and reveal the appropriate treatment strategy for each patient.

tumor monitoring and also discovery of new therapies for these patients.

this transmembrane hematopoietic stem cell glycoprotein.

148 Human Skin Cancers - Pathways, Mechanisms, Targets and Treatments

potential therapeutic targets in skin SCC.

suppressed patients.

and cell adhesion proteins.

This paper is partly supported by grants PNII-PT-PCCA-2013-4-1386 (Project 185/2014) and PN-II-PT-PCCA-2013-4-1407 (Project 190/2014) financed by Executive Agency for Higher Education, Research, Development and Innovation.
