Autor: |
Yan-Xia Wang, Haibo Wu, Yong Ren, Shengqing Lv, Chengdong Ji, Dongfang Xiang, Mengsi Zhang, Huimin Lu, Wenjuan Fu, Qing Liu, Zexuan Yan, Qinghua Ma, Jingya Miao, Ruili Cai, Xi Lan, Bin Wu, Wenying Wang, Yinhua Liu, Dai-Zhong Wang, Mianfu Cao, Zhicheng He, Yu Shi, Yifang Ping, Xiaohong Yao, Xia Zhang, Peng Zhang, Ji Ming Wang, Yan Wang, Youhong Cui, Xiu-Wu Bian |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-15 (2022) |
Druh dokumentu: |
article |
ISSN: |
2059-3635 |
DOI: |
10.1038/s41392-022-00890-7 |
Popis: |
Abstract Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options. The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity. In the present study, we demonstrate that Kir2.1, an inwardly-rectifying potassium channel, is highly expressed in non-WNT/SHH MBs, which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway. Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice. Moreover, Kir2.1high/nuclear N2ICDhigh MBs are associated with the significantly shorter lifespan of the patients. Thus, Kir2.1high/nuclear N2ICDhigh can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs. Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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