445 Does tyrosine and serine phosphorylation of STAT3 drive cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa?

The early onset of aggressive cutaneous squamous cell carcinoma (cSCC) and its rapid progression in recessive dystrophic epidermolysis bullosa (RDEB) leads to premature mortality. Elevated levels STAT3Tyr705 (pY-STAT3) phosphorylation have been demonstrated RDEB-derived cSCC cells, showing that constitutive activation dysregulation the pathway play a role RDEB-cSCC pathogenesis. Application Ruxolitinib (JAK1/2 inhibitor) an xenograph mouse model, reduces size small tumours but is insufficient completely reduce bigger tumours. We hypothesized STAT3 at Serine 727 (pS-STAT3) might tumour progression. Recently, pS-STAT3 has shown be relevant for evolution some cancers it not yet studied RDEB-cSCC. To test our hypothesis, we patient samples with different degrees de-differentiation (RDEB skin, edge center RDEB-cSCC). pY-STAT3 was preferentially upregulated normal RDEB followed by edge, lowest expression centre. In contrast, presented opposite pattern: more less skin. looked further into JAK/STAT using Taqman array Reactome. Three pathways were differentially expressed: MAPK, RAF antigen B receptor activation, RDEB-SCC on investigate analyse cancer progression, generated spheroid vitro model which is: easy generate; requires minimal cell; suitable drug testing; can recapitulate stages. able control their use them testing: decreased 20% after 6 days treatment. This new 3D along analysis human allow us better understand signalling