Logo image
Back
O-GlcNAc Transferase Regulates Cancer Stem-like Potential of Breast Cancer Cells
Journal article   Open access   Peer reviewed

O-GlcNAc Transferase Regulates Cancer Stem-like Potential of Breast Cancer Cells

Neha M Akella, Giang Le Minh, Lorela Ciraku, Ayonika Mukherjee, Zachary A Bacigalupa, Dimpi Mukhopadhyay, Valerie L Sodi and Mauricio J Reginato
Molecular cancer research, v 18(4), pp 585-598
Apr 2020
DOI: https://doi.org/10.1158/1541-7786.MCR-19-0732
PMID: 31974291
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1158/1541-7786.mcr-19-0732View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.1158/1541-7786.MCR-19-0732View
Published, Version of Record (VoR) Open

Abstract

Animals Breast Neoplasms - enzymology Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Line, Tumor Female Heterografts Humans MCF-7 Cells Mice Mice, Inbred NOD Mice, SCID N-Acetylglucosaminyltransferases - genetics N-Acetylglucosaminyltransferases - metabolism Neoplastic Stem Cells - enzymology Neoplastic Stem Cells - pathology
Breast tumors are heterogeneous and composed of different subpopulation of cells, each with dynamic roles that can change with stage, site, and microenvironment. Cellular heterogeneity is, in part, due to cancer stem-like cells (CSC) that share properties with stem cells and are associated with treatment resistance. CSCs rewire metabolism to meet energy demands of increased growth and biosynthesis. O-GlcNAc transferase enzyme (OGT) uses UDP-GlcNAc as a substrate for adding O-GlcNAc moieties to nuclear and cytoplasmic proteins. OGT/O-GlcNAc levels are elevated in multiple cancers and reducing OGT in cancer cells blocks tumor growth. Here, we report that breast CSCs enriched in mammosphere cultures contain elevated OGT/O-GlcNAcylation. Inhibition of OGT genetically or pharmacologically reduced mammosphere forming efficiency, the CD44 /CD24 , NANOG+, and ALDH+ CSC population in breast cancer cells. Conversely, breast cancer cells overexpressing OGT increased mammosphere formation, CSC populations , and also increased tumor initiation and CSC frequency . Furthermore, OGT regulates expression of a number of epithelial-to-mesenchymal transition and CSC markers including CD44, NANOG, and c-Myc. In addition, we identify Krüppel-like factor 8 (KLF8) as a novel regulator of breast cancer mammosphere formation and a critical target of OGT in regulating CSCs. IMPLICATIONS: These findings demonstrate that OGT plays a key role in the regulation of breast CSCs and tumor initiation , in part, via regulation of KLF8, and thus inhibition of OGT may serve as a therapeutic strategy to regulate tumor-initiating activity.

Metrics

8 Record Views
50 citations in Web of Science
52 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Cell Biology
Oncology
Logo image