MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma
dc.contributor.author | Ranjan, Atul | |
dc.contributor.author | Iyer, Swathi V. | |
dc.contributor.author | Ward, Christopher | |
dc.contributor.author | Link, Tim | |
dc.contributor.author | Diaz, Francisco J. | |
dc.contributor.author | Dhar, Animesh | |
dc.contributor.author | Tawfik, Ossama W. | |
dc.contributor.author | Weinman, Steven A. | |
dc.contributor.author | Azuma, Yoshiaki | |
dc.contributor.author | Izumi, Tadahide | |
dc.contributor.author | Iwakuma, Tomoo | |
dc.date.accessioned | 2018-06-13T16:34:48Z | |
dc.date.available | 2018-06-13T16:34:48Z | |
dc.date.issued | 2018-04-20 | |
dc.identifier.citation | Ranjan, A., Iyer, S. V., Ward, C., Link, T., Diaz, F. J., Dhar, A., … Iwakuma, T. (2018). MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma. Oncotarget, 9(30), 21429–21443. http://doi.org/10.18632/oncotarget.25117 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/26497 | |
dc.description.abstract | Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation of Elk-1 and decreases mRNA expression of Elk-1 target genes. Reduced Elk-1 activity is caused by inhibited nuclear translocation of phosphorylated Erk1/2 (p-Erk) by MTBP and subsequent inhibition of Elk-1 phosphorylation. We also reveal that MTBP inhibits the interaction of p-Erk with importin-7/RanBP7 (IPO7), an importin family member which shuttles p-Erk into the nucleus, by binding to IPO7. Moreover, high levels of MTBP in human HCC tissues are correlated with cytoplasmic localization of p-Erk1/2. Our study suggests that MTBP suppresses metastasis, at least partially, by down-modulating the Erk1/2-Elk-1 signaling pathway, thus identifying a novel regulatory mechanism of HCC metastasis by regulating the subcellular localization of p-Erk. | en_US |
dc.publisher | Impact Journals | en_US |
dc.rights | Copyright © 2018 Ranjan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/ | en_US |
dc.subject | MDM2 | en_US |
dc.subject | MTBP | en_US |
dc.subject | Erk1/2 | en_US |
dc.subject | Elk-1 | en_US |
dc.subject | Metastasis | en_US |
dc.title | MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Azuma, Yoshiaki | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.18632/oncotarget.25117 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's license is described as: Copyright © 2018 Ranjan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.