| Autor: |
Bin He, Rui Gao, Shasha Lv, Ailin Chen, Junxiu Huang, Luoxuan Wang, Yunxiu Feng, Jiesi Feng, Bing Liu, Jie Lei, Bing Deng, Bai Cui, Fei Peng, Min Yan, Zifeng Wang, Eric W-F Lam, Bilian Jin, Zhiming Shao, Yulong Li, Jianwei Jiao, Xi Wang, Quentin Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 8, Iss 1, Pp 1-19 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-023-01487-4 |
| Popis: |
Abstract Cancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity. Specifically, neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis, where ATF1 serves as a conserved hub. Upon activation by norepinephrine, ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thereby orchestrating nuclear reprograming and mitochondrial rejuvenating. Accordingly, single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells. These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program, suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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