論文 - 詳細
| RRC ID | 73019 |
|---|---|
| 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. |
| タイトル | HES1 promoter activation dynamics reveal the plasticity, stemness and heterogeneity in neuroblastoma cancer stem cells. |
| ジャーナル | 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. |
| 巻・号 | 135(22) |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | IMR-32(RCB1895) |