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dc.contributor.advisorGöktuna, Serkan İsmail
dc.contributor.authorUygur, Beste
dc.date.accessioned2021-02-15T06:47:13Z
dc.date.available2021-02-15T06:47:13Z
dc.date.copyright2021-01
dc.date.issued2021-01
dc.date.submitted2021-02-11
dc.identifier.urihttp://hdl.handle.net/11693/55128
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2021.en_US
dc.descriptionIncludes bibliographical references (leaves 105-128).en_US
dc.description.abstractColorectal carcinoma is a heterogeneous disease which is the third leading cause of cancer-associated mortalities in the world. It is also reported to be the third most diagnosed cancer among other cancer types. The intracellular functions of purines and pyrimidines in energy transaction and nucleic acid synthesis reactions have been well-known and clarified. Notwithstanding, the extracellular roles played by purinergic signaling components in cancer initiation and progression was not disclosed thoroughly as yet and become more prominent day by day. The extracellular purinergic system may have growth-inhibiting or growth-promoting effects in tumors in a tissue and context-dependent manner. Indeed, the knowledge regarding the impact of these elements in colorectal cancer is immensely limited. Therefore, in this study, we focused on deciphering the involvement of several extracellular purinergic signaling components in colorectal cancer, which are mainly one of the enzymes involved in degradation process of ATP, PSE002, and one of the adenosine receptors, PSC003. To assess their roles in colorectal cancer, we generated stable knockout cell lines targeting these two genes separately by CRISPR/Cas9 gene editing as well as transiently depleted cell lines by RNA interference (RNAi). The depletion of PSE002 and also PSC003 promoted cell proliferation and their anchorage-independent growth in vitro. In addition to this, their loss resulted in enhanced epithelial-to-mesenchymal transition (EMT) by upregulating the expression of mesenchymal markers. Moreover, cell line-derived xenograft models (CDX) of PSE002 could corroborate in vitro findings and strikingly augmented tumor growth in vivo. Interestingly, the effects observed in colorectal cancer cell lines upon PSE002 silencing could not be seen upon pharmacological inhibition by PSE002-selective antagonist. Contrary to this, PSC003-selective antagonist led to increased proliferative capacity in colorectal cancer cell lines under normal or hypoxic conditions. Ultimately, our findings provide a different perspective to extracellular adenosine signaling and claim that these targets act as tumor suppressor genes in colorectal carcinoma which should be taken into consideration for selecting therapeutic strategies against colorectal cancer.en_US
dc.description.statementofresponsibilityby Beste Uyguren_US
dc.format.extentxviii, 149 leaves : color illustrations, charts, graphics ; 30 cm.en_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectPurinergic signalingen_US
dc.subjectColorectal canceren_US
dc.subjectCRISPR/Cas9en_US
dc.subjectEctonucleotidaseen_US
dc.subjectAdenosine receptorsen_US
dc.subjectAdenosine signalingen_US
dc.titleCharacterization of extracellular purinergic signaling components in colorectal carcinomaen_US
dc.title.alternativeHücreler arası pürinerjik sinyalizasyon bileşenlerinin kolorektal karsinomda karakterizasyonuen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreeM.S.en_US
dc.identifier.itemidB151910
dc.embargo.release2021-08-10


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