RRC ID 73019
Author Riya PA, Basu B, Surya S, Parvathy S, Lalitha S, Jyothi NP, Meera V, Jaikumar VS, Sunitha P, Shahina A, Sukumaran R, Nair AS, Dhanesh SB, Jiffy J, Nelson-Sati S, Maliekal TT, Das AV, James J.
Title HES1 promoter activation dynamics reveal the plasticity, stemness and heterogeneity in neuroblastoma cancer stem cells.
Journal J Cell Sci
Abstract Notch signaling and its downstream target, HES1, play a critical role in regulating and maintaining cancer stem cells (CSCs), similar to embryonic development. Here, we report a unique subclass of Notch Independent Hes-1(NIHes-1) expressing Cancer Stem Cells (CSCs) in neuroblastoma. These CSCs maintain sustained HES1 expression by activation of HES1 promoter region upstream of classical CBF-1 binding sites thereby, completely bypassing Notch receptor mediated activation. These stem cells have self-renewal ability and potential to generate tumor. Interestingly, we observed that NIHes-1 CSCs could transit to Notch dependent Hes-1 expressing (NDHes-1) CSCs where HES1 is expressed by Notch receptor mediated promoter activation. We observed that NDHes-1 expressing CSCs also had the potential to transit to NIHes-1 CSCs and during this coordinated bidirectional transition, both CSCs gave rise to the majority of the bulk cancer cells, which had HES1 promoter inactive (PIHes-1). A few of these PIHes-1 cells were capable of reverting to a CSC state. These findings explain the existence of heterogenic mode of Hes-1 promoter activation within IMR-32 and the potential to switch between them.
Volume 135(22)
Published 2022-11-15
DOI 10.1242/jcs.260157
PII 280135
PMID 36321463
MeSH Basic Helix-Loop-Helix Transcription Factors* / genetics Basic Helix-Loop-Helix Transcription Factors* / metabolism Cell Line Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Neoplastic Stem Cells / metabolism Neuroblastoma* / genetics Neuroblastoma* / metabolism Promoter Regions, Genetic / genetics Receptors, Notch / metabolism Transcription Factor HES-1 / genetics Transcription Factor HES-1 / metabolism
IF 4.573
Human and Animal Cells IMR-32(RCB1895)