The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells

Simple item page
atmire.migration.oldid4807
dc.contributor.advisorRiabowol, Karl Jr
dc.contributor.authorWang, Fangwu Jr
dc.contributor.committeememberSenger, Donna Jr
dc.contributor.committeememberCobb, Jennifer Jr
dc.contributor.committeememberRancourt, Derrick Jr
dc.date.accessioned2016-08-31T14:44:46Z
dc.date.available2016-08-31T14:44:46Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractBrain tumor initiating cells (BTICs) are believed to account for the recurrence of glioblastomas following treatment. Recent studies have shown that the stemness of BTICs and intratumoral differentiation hierarchy are determined largely on the epigenetic level. The ING family of epigenetic regulators function in diverse growth regulatory, metastasis and chemoresistance pathways, through targeting different histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes to the H3K4me3 mark to alter histone acetylation. ING5, a stoichiometric unit of three HAT complexes, has been directly implicated in the maintenance of epidermal stem cells. Here we found that ING5 was highly expressed in BTICs and rapidly downregulated upon in vitro differentiation. Ectopic expression of ING5 promoted self-renewal, prevented lineage differentiation and increased the stem cell pool in the BTIC population, accompanied by an elevated expression of stem cell core transcription factors OCT4, OLIG2 and Nestin. ING5 enhanced the activity of the PI3K/AKT and MEK/ERK pathways in the absence of growth factors to sustain self-renewal of BTICs over serial sphere passage. Transcriptome analysis indicated ING5 was an inducer of the intracellular calcium signaling and follicle stimulating hormone pathways, which were confirmed to co-operatively enhance the self-renewal of BTICs. This study identifies ING5 as a positive regulator of BTIC stem cell character, whose expression negatively correlates with patient prognosis, especially in the Proneural subtype and tumors with low SOX2 expression, therefore suggesting that altering histone acetylation status and the signaling pathways induced by ING5 may provide useful clinical targets to reduce recurrence in glioblastoma.en_US
dc.identifier.citationWang, F. J. (2016). The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28327en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28327
dc.identifier.urihttp://hdl.handle.net/11023/3233
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Cell
dc.subjectBiology--Molecular
dc.subjectBiochemistry
dc.subject.classificationglioblastomaen_US
dc.subject.classificationcancer stem cellsen_US
dc.subject.classificationINGen_US
dc.subject.classificationstemnessen_US
dc.titleThe Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells
dc.typemaster thesis
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ucalgary_2016_wang_fangwu.pdf
Size:
7.93 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Open Theses and Dissertations