Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49489
Title: ST3GAL1 SIALYLTRANSFERASE MEDIATES INVASIVENESS AND TUMORIGENICITY IN GLIOMA-PROPAGATING CELLS AND ASSOCIATES WITH PATIENT SURVIVAL OUTCOME AND DISEASE PROGRESSION
Authors: CHONG YUK KIEN
Keywords: ST3Gal1 sialyltransferase, glioma, glioma-propagating cell, FoxM1, TGFβ, Connectivity Map
Issue Date: 26-Sep-2013
Source: CHONG YUK KIEN (2013-09-26). ST3GAL1 SIALYLTRANSFERASE MEDIATES INVASIVENESS AND TUMORIGENICITY IN GLIOMA-PROPAGATING CELLS AND ASSOCIATES WITH PATIENT SURVIVAL OUTCOME AND DISEASE PROGRESSION. ScholarBank@NUS Repository.
Abstract: Cell surface sialylation confers various roles in cancer including proliferation, invasiveness and metastasis. However, the molecular mechanisms of ST3Gal1 sialyltransferase in mediating malignant glioma progression remain poorly defined. We demonstrate that ST3Gal1 sialyltransferase marks a self-renewing fraction in patient-derived glioma cells, and its depletion prolongs survival in an orthotopic mouse model. Using a patient-centric bioinformatics approach, we found that active TGF? signaling induces ST3GAL1 and correlates with ST3Gal1 activation in patient tumors with the mesenchymal molecular profile. As gene expression drives brain tumor disease progression, we further examined differentially expressed genes from ST3GAL1-knocked down cells, and identified FoxM1 as a downstream effector. Importantly, we show that ST3Gal1 mediates the glioma phenotype through inhibition of FoxM1 protein degradation, which in turn is regulated by the anaphase-promoting complex/cyclosome (APC/C)-Cdh1 complex. We propose that ST3Gal1 represents an amenable target for the development of efficacious therapeutics.
URI: http://scholarbank.nus.edu.sg/handle/10635/49489
Appears in Collections:Ph.D Theses (Open)

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