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Generation of anti-tumorigenic MET receptor variants by splicing interference
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Rathod, Trushar. Generation of anti-tumorigenic MET receptor variants by splicing interference. Retrieved from https://doi.org/doi:10.7282/t3-jzv7-qa62

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TitleGeneration of anti-tumorigenic MET receptor variants by splicing interference
NameRathod, Trushar (author); Suh, Nanjoo (chair); Cartegni, Luca (internal member); Zhou, Renping (internal member); Scaltriti, Maurizio (outside member); Rutgers University; School of Graduate Studies
Date Created2019
Other Date2019-05 (degree)
SubjectPharmacology, Cellular and Molecular, Hepatocyte growth factor -- Receptors
Extent1 online resource (xviii, 154 pages) : illustrations
DescriptionAberrant activation of MET, a receptor tyrosine kinase (RTK), leads to tumor growth, invasion and metastasis and is implicated in multiple types of cancers. Hence, various strategies have been employed to target MET for cancer therapy including recombinant form of MET ectodomain to sequester ligand and suppress MET activity. Here, we describe multiple C-terminal truncated MET decoys receptors (sdMET) with therapeutic potential. We show that these sdMET isoforms are translated from stable mRNA variants which are generated via Intronic polyadenylation (IPA) of MET’s pre-mRNA in a U1-snRNP (U1) dependent manner. Moreover, we demonstrate increase in sdMET IPA isoforms of choice at expense of full-length MET with our antisense-based strategy by blocking U1 binding to specific 5’ splice site and activating downstream intronic poly (A) site. Our strategy is an improvement of current methods due to its two-pronged approach: suppress MET activity in targeted cells by converting oncogenic MET into soluble decoy to have dominant negative effect on surround microenvironment in paracrine manner.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-jzv7-qa62
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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