Please use this identifier to cite or link to this item: https://doi.org/10.1002/path.5848
Title: EHMT1 promotes tumor progression and maintains stemness by regulating ALDH1A1 expression in alveolar rhabdomyosarcoma
Authors: Nachiyappan, Alamelu 
Soon, Joshua Ling Jun 
Lim, Huey Jin
Lee, Victor KM 
Taneja, Reshma 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Pathology
stem cells
skeletal muscle
differentiation
C/EBP beta
C/EBP-BETA
ALDEHYDE DEHYDROGENASE
METHYLTRANSFERASES G9A
PROTEIN
CELLS
METHYLATION
PAX3-FOXO1
MYOGENESIS
PATHWAY
MARKER
Issue Date: 10-Jan-2022
Publisher: WILEY
Citation: Nachiyappan, Alamelu, Soon, Joshua Ling Jun, Lim, Huey Jin, Lee, Victor KM, Taneja, Reshma (2022-01-10). EHMT1 promotes tumor progression and maintains stemness by regulating ALDH1A1 expression in alveolar rhabdomyosarcoma. JOURNAL OF PATHOLOGY 256 (3) : 349-362. ScholarBank@NUS Repository. https://doi.org/10.1002/path.5848
Abstract: Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with poor prognosis. Cancer stem cells (CSCs) are seeds for tumor relapse and metastasis. However, pathways that maintain stemness genes are not fully understood. Here, we report that the enzyme euchromatic histone lysine methyltransferase 1 (EHMT1) is expressed in primary and relapse ARMS tumors. EHMT1 suppression impaired motility and induced differentiation in ARMS cell lines and reduced tumor progression in a mouse xenograft model in vivo. RNA sequencing of EHMT1-depleted cells revealed downregulation of ALDH1A1 that is associated with CSCs. Consistent with this, inhibition of ALDH1A1 expression and activity mimicked EHMT1 depletion phenotypes and reduced tumorsphere formation. Mechanistically, we demonstrate that EHMT1 does not bind to the ALDH1A1 promoter but activates it by stabilizing C/EBPβ, a known regulator of ALDH1A1 expression. Our findings identify a role for EHMT1 in maintenance of stemness by regulating ALDH1A1 expression and suggest that targeting ALDH+ cells is a promising strategy in ARMS. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Source Title: JOURNAL OF PATHOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/226557
ISSN: 00223417
10969896
DOI: 10.1002/path.5848
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