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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1007/bf01274405

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ISSN

1573-4919

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Antagonizing canonical Wnt signaling pathway by re

Authors: Archita Ghoshal Siddhartha Sankar Ghosh
Publish Date: 2016/06/23
Volume: 418, Issue: 1-2, Pages: 119-135
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Abstract

The Wnt signaling pathway plays a predominant role in aberrant proliferation in myriad of cancers In noncancerous cells Wnts are blocked by the secreted frizzledrelated proteins sFRPs that are generally downregulated in cancer cells We have purified and characterized bacterially expressed glutathione Stransferasetagged SFRP4 from a novel clone generated from human cell origin Cervical cancer HeLa and lung cancer A549 cells in which Wnt and associated genes were found to be expressed were treated with the purified recombinant sFRP4 which revealed a significant dosedependent cell growth inhibition up to 40  The current investigation on functionality of this bacterially produced recombinant sFRP4 in arresting cancer cell proliferation is the first of its kind where G2/M phase arrest and early apoptosis were evident Increase in phosphorylated βcatenin in sFRP4 treatment indicated inhibition of Wnt pathway which was further confirmed by downregulation of proproliferative genes namely cyclin D1 cmyc and survivin Functional activity of recombinant sFRP4 was further exploited in cotherapy module with chemotherapeutic drugs to decipher molecular events Collectively our study on purified recombinant sFRP4 from bacterial host holds great promise in targeting Wnt signaling for exploring new strategies to combat cancer

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