Suman, Prabhat2020-08-212024-08-142020-08-212024-08-142018Suman, Prabhat & Chander, Harish (2018) Transcriptional Regulation of Pro-metastatic Protein Formin Binding Protein17 (FBP17) in Breast Cancerhttp://10.2.3.109/handle/32116/2743Breast cancer is a diverse disease with multiple subtypes. Among the different molecular subtypes, triple negative breast cancers (TNBC) harbor frequent mutation in tumor suppressor p53. Recently it was shown that p53 suppresses Transducer of Cdc42-dependent Actin assembly-1 (Toca-1) that belongs to CIP4 subfamily. Members of the family including FBP17 play a significant role in actin assembly. FBP17 and Toca-1 have been recognized as key scaffolds for recruiting actin regulatory protein to promote invadopodia formation. Metastatic cancer cells form invadopodia and the F-BAR proteins are shown to enhance invadopodia. FBP17 consists of F-BAR domain, Cdc-15 homology, putative Rho-binding domain and SH3 domain. In the present study, we elucidate the correlation between p53 and FBP17 that affects metastatic potential of cancer cells. We observed that cancer cell lines with mutated p53 have high levels of FBP17. Activation of wild type p53 reduces FBP17 both at mRNA and protein level. Further, the ectopic expression of wild type p53 reduces FBP17 whereas mutant p53 failed to do so. Different cell lines and different methods of p53 activation were used to study the p53-FBP17 axis. Chromatin immunoprecipitation studies revealed the binding of p53 in the promoter of FBP17. The metastatic potential of breast cancer cells was observed after double knock down of both p53 and FBP17. Interestingly, we found that combined silencing of these two proteins led to a partial rescue of invasion upon p53 silencing in vitro. In conclusion we suggest that p53 controls FBP17 expression and FBP17 contributes to the invasion of cancer cells upon loss of p53 activity in cancer.en-USBreast cancerFBP17tumor suppressor p53InvasionInvadopodiaTranscriptionThesisT00868