In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4470-4470
Abstract:
Cell surface sialylation has been associated with tumor cell invasiveness in several cancers. Patients with grade IV glioblastoma multiforme (GBM) often show a median survival period of fifteen months, even with the current standard-of-care treatment. Among the reasons for this poor prognosis lies in the cellular and molecular heterogeneity of tumor cells. The Cancer Genome Atlas efforts have shown that histologically identical GBM tumors can be divided into four molecular subtypes based on gene expression, with each subtype corresponding to unique genomic aberrations and clinical outcome. These findings highlight the limitation of relying solely on morphological approaches to diagnose and subsequently treat patients. We conducted a lectin screen with the goal of identifying candidates that stained normal and tumor cells differentially. We identified a sialyltransferase, ST3Gal1 as a mediator of the binding pattern of one such lectin, Peanut Agglutinin. We demonstrate that ST3Gal1 promotes tumor cell invasiveness and enriches for self-renewal potential in the mesenchymal tumor subclass of patients, typified by highly aggressive and recurrent profiles. Depletion of ST3Gal1 extends tumor latency and prolongs survival in mice. Importantly, an enrichment of the ST3GAL1 transcriptomic program portends poor prognosis in glioma patients. Moving forward, since there are no mutations or changes in copy number of ST3GAL1, we explored epigenetic regulation as a possible mechanism. By tapping into data from the NIH Roadmap Epigenome, and transcriptomic analysis of our patient tumor-derived cells, we identified a histone clustering signature that correlates with survival outcome and disease progression. We are currently investigating one such histone modifier, lysine (K)-specific demethylase 1A (LSD1) and its role at modifying ST3GAL1 transcription and activity. Citation Format: Yuk Kien Chong, Edwin Sandanaraj, Lynnette Koh, Moogaambikai Thangaveloo, Melanie SY Tan, Geraldene Koh, Tan Boon Toh, Grace GY Lim, Joanna Holbrook, Oi Lian Kon, Mahendran Nadarajah, Ivan Ng, Wai Hoe Ng, Nguan Soon Tan, Kah Leong Lim, Carol S. Tang, Beng Ti Ang. ST3GAL1-associated transcriptomic program portends poor prognosis in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4470.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-4470
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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