American Association for Cancer Research
Browse
15417786mcr170105-sup-179490_2_supp_4036752_bpvdb2.pdf (85.17 kB)

Supplementary Table 1 from MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation

Download (85.17 kB)
journal contribution
posted on 2023-04-03, 17:07 authored by Hailong Liu, Qianwen Sun, Youliang Sun, Junping Zhang, Hongyu Yuan, Shuhuan Pang, Xueling Qi, Haoran Wang, Mingshan Zhang, Hongwei Zhang, Chunjiang Yu, Chunyu Gu

Table S1. Univariate and multivariate analysis by Cox proportional model.

Funding

Beijing Commission of Education

Beijing Municipal Science & Technology Commission

National Nature Science Foundation of China

History

ARTICLE ABSTRACT

Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK- or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stem-like cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients.Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275–86. ©2017 AACR.

Usage metrics

    Molecular Cancer Research

    Categories

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC