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Transcriptional Regulation of Pro metastatic Protein Formin Binding Protein17 FBP17 in Breast Cancer

Shodhganga@INFLIBNET

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Title Transcriptional Regulation of Pro metastatic Protein Formin Binding Protein17 FBP17 in Breast Cancer
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Contributor Chander, Harish
 
Subject Breast cancer, FBP17, tumor suppressor p53, Invasion, Invadopodia, Transcription
 
Description Breast cancer is a diverse disease with multiple subtypes. Among the different molecular
newlinesubtypes, triple negative breast cancers (TNBC) harbor frequent mutation in tumor suppressor
newlinep53. Recently it was shown that p53 suppresses Transducer of Cdc42-dependent Actin
newlineassembly-1 (Toca-1) that belongs to CIP4 subfamily. Members of the family including FBP17 play
newlinea significant role in actin assembly. FBP17 and Toca-1 have been recognized as key scaffolds
newlinefor recruiting actin regulatory protein to promote invadopodia formation. Metastatic cancer cells
newlineform invadopodia and the F-BAR proteins are shown to enhance invadopodia. FBP17 consists of
newlineF-BAR domain, Cdc-15 homology, putative Rho-binding domain and SH3 domain. In the present
newlinestudy, we elucidate the correlation between p53 and FBP17 that affects metastatic potential of
newlinecancer cells. We observed that cancer cell lines with mutated p53 have high levels of FBP17.
newlineActivation of wild type p53 reduces FBP17 both at mRNA and protein level. Further, the ectopic
newlineexpression of wild type p53 reduces FBP17 whereas mutant p53 failed to do so. Different cell
newlinelines and different methods of p53 activation were used to study the p53-FBP17 axis. Chromatin
newlineimmunoprecipitation studies revealed the binding of p53 in the promoter of FBP17. The metastatic
newlinepotential of breast cancer cells was observed after double knock down of both p53 and FBP17.
newlineInterestingly, we found that combined silencing of these two proteins led to a partial rescue of
newlineinvasion upon p53 silencing in vitro. In conclusion we suggest that p53 controls FBP17 expression
newlineand FBP17 contributes to the invasion of cancer cells upon loss of p53 activity in cancer
newline
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Date 2018-10-16T06:49:52Z
2018-10-16T06:49:52Z
10/08/2015
17/09/2018
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Type Ph.D.
 
Identifier http://hdl.handle.net/10603/218682
 
Language English
 
Relation —
 
Rights university
 
Format —
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DVD
 
Coverage —
 
Publisher Bathinda
Central University of Punjab
Department of Human Genetics and Molecular Medicine
 
Source University