| 著者 |
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.
|
| 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.
|
