Notch1/p21/Ask1 axis in skin cancer development
Componente | Categoria |
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Federica Truglio | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca |
Nonmelanoma skin cancer (NMSC) represents the most common form of skin cancer, its incidence has been reported significantly increased up to 10% per annum, and currently 2-3 million new cases of NMSC are diagnosed worldwide every year. Despite mortality from NMSC is low, it is associated with significant morbidity and cost suggesting that knowledge of molecular basis underlying its formation are needed to improve prevention and clinical treatments.
Notch signaling is an important form of intracellular communication and plays a key role in cell fate determination and differentiation and its dysregulation gives rise various disease including cancer. However, in tumorigenesis its role remains unclear, indeed in skin cancer Notch1 may have dual role; specifically, in skin context, many reports supported a role of Notch1 as tumor suppressor or oncogene suggesting its ability to induce different responses dependent on crosstalk with other signaling pathways.
p21 is well-known cell cycle inhibitor and it is a Notch1 downstream target involved in induction of differentiation in mouse keratinocytes. Furthermore, p21 has a key function in tumor promotion because it can protect cells against apoptosis binding proteins involved in induction of this process and inhibiting their activity, among the others Ask1.
Because the transformation of epithelial cells depends on the deregulation of normal differentiation, the present proposal is aimed to investigate if the activity of Notch signaling, through the regulation of Ask1 by p21, can be modified to promote one response over another activating specific mechanism that in cancer cells may be selected as a strategy to enhance the malignant phenotype in keratinocyte cancerogenesis.