Please use this identifier to cite or link to this item:
https://doi.org/10.1038/s41388-021-01661-4
DC Field | Value | |
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dc.title | MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma | |
dc.contributor.author | Ke, Xin-Yu | |
dc.contributor.author | Chen, Ye | |
dc.contributor.author | Tham, Valarie Yu-Yan | |
dc.contributor.author | Lin, Ruby Yu-Tong | |
dc.contributor.author | Dakle, Pushkar | |
dc.contributor.author | Nacro, Kassoum | |
dc.contributor.author | Puhaindran, Mark Edward | |
dc.contributor.author | Houghton, Peter | |
dc.contributor.author | Pang, Angela | |
dc.contributor.author | Lee, Victor Kwanmin | |
dc.contributor.author | Ding, Ling-Wen | |
dc.contributor.author | Gery, Sigal | |
dc.contributor.author | Hill, Jeffrey | |
dc.contributor.author | Chen, Leilei | |
dc.contributor.author | Xu, Liang | |
dc.contributor.author | Koeffler, H Phillip | |
dc.date.accessioned | 2021-11-24T05:33:16Z | |
dc.date.available | 2021-11-24T05:33:16Z | |
dc.date.issued | 2021-02-09 | |
dc.identifier.citation | Ke, Xin-Yu, Chen, Ye, Tham, Valarie Yu-Yan, Lin, Ruby Yu-Tong, Dakle, Pushkar, Nacro, Kassoum, Puhaindran, Mark Edward, Houghton, Peter, Pang, Angela, Lee, Victor Kwanmin, Ding, Ling-Wen, Gery, Sigal, Hill, Jeffrey, Chen, Leilei, Xu, Liang, Koeffler, H Phillip (2021-02-09). MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma. ONCOGENE 40 (10) : 1851-1867. ScholarBank@NUS Repository. https://doi.org/10.1038/s41388-021-01661-4 | |
dc.identifier.issn | 09509232 | |
dc.identifier.issn | 14765594 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/207816 | |
dc.description.abstract | Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment. | |
dc.language.iso | en | |
dc.publisher | SPRINGERNATURE | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Oncology | |
dc.subject | Cell Biology | |
dc.subject | Genetics & Heredity | |
dc.type | Article | |
dc.date.updated | 2021-11-24T03:25:45Z | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | PATHOLOGY | |
dc.description.doi | 10.1038/s41388-021-01661-4 | |
dc.description.sourcetitle | ONCOGENE | |
dc.description.volume | 40 | |
dc.description.issue | 10 | |
dc.description.page | 1851-1867 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.pdf | 5.97 MB | Adobe PDF | OPEN | Published | View/Download |
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