MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma.

Oncotarget
Atul RanjanT Iwakuma

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 s...Continue Reading

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Citations

Mar 13, 2019·International Journal of Molecular Sciences·Galia Maik-RachlineRony Seger
Aug 23, 2019·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Qiu-Ting LiZhi-Fan Xiong
Feb 16, 2021·Frontiers in Oncology·Tongyue ZhangLimin Xia

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Methods Mentioned

BETA
surgical resection
nuclear translocation
co-immunoprecipitation
Assay

Software Mentioned

Graph Pad Prism
Stata

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