Principal Investigator - Rosemary Akhurst
TGF-β signaling is implicated in formation and maintenance of a cancer stem cell-like (CSC) phenotype that plays a central role in driving tumor metastasis, recurrence and drug resistance. We demonstrated that down-stream TGFβ signaling might be activated independently of the TGFβ receptors. The hypothesis to be tested is that kinases other than TGFβRII, TGFβR1, ACVR1b and ACVR1c can phosphorylate and activate canonical targets of the proximal TGFβ signaling pathway, Smad2 and Smad3, to independently drive carcinoma cells towards the CSC phenotype.
Translational potential: Identification of druggable kinases that would target the breast CSC.
The specific aims of the current project are:
Significance: This project may provide new insights into the molecular regulation of CSC maintenance by TGF-β and might provide novel druggable targets for attacking CSCs.