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USF Tampa Graduate Theses and Dissertations

2021

Amoeboid

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Metastatic Mat Phenotype Driven By Noncanonical Epha2 Signaling In Melanoma, Chao Zhang Nov 2021

Metastatic Mat Phenotype Driven By Noncanonical Epha2 Signaling In Melanoma, Chao Zhang

USF Tampa Graduate Theses and Dissertations

Acquired BRAF/MAPK/extracellular signal‒regulated kinase inhibitor resistance in melanoma results in a new transcriptional state associated with an increased risk of metastasis. In this study, we identified noncanonical ephrin receptor (Eph) EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry‒based proteomic and phenotypic assays to demonstrate that the expression of active noncanonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition driven by Cdc42 activation. The induction of mesenchymal-to-amoeboid transition promoted melanoma cell invasion, survival under shear stress, adhesion to endothelial cells under continuous-flow conditions, increased permeability of endothelial cell monolayers, and stimulated melanoma transendothelial cell …