Phase 1 study of safety, pharmacokinetics, and pharmacodynamics of tivantinib in combination with bevacizumab in adult patients with advanced solid tumors

Maguire, William F.; Schmitz, John C.; Scemama, Jonas; Czambel, Ken; Yc, Lin; Green, Anthony G.; Wu, Shaoyu; Lin, Hailong; Puhalla, Shannon; Rhee, John C.; Stoller, Ronald G.; Tawbi, Hussein A.; Lee, James J.; Wright, John J.; Beumer, Jan H.; Chu, Edward; Appleman, Leonard Joseph; Team, Etctn Study

doi:10.1007/s00280-021-04317-y

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…In this study, the transcription factor activity of ETS-1 was detected by luciferase and qPCR assay, and the recruitment of ETS-1 in the promoter region of its downstream gene mmp1 could also directly reflect the effects of MTBP on ETS-1. The role of ETS-1 in HCC has been widely reported ( 88 , 89 ). It is worth mentioning that the inhibitor of ETS-1 used in this study was ARQ-197, which is an inhibitor of c-MET ( 88 , 89 ).…”

Section: Discussionmentioning

confidence: 99%

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MTBP enhances the activation of transcription factor ETS-1 and promotes the proliferation of hepatocellular carcinoma cells

Wang

Chu

et al. 2022

Front. Oncol.

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Increasing evidence indicates that the oncoprotein murine double minute (MDM2) binding protein (MTBP) can be considered a pro-oncogene of human malignancies; however, its function and mechanisms in hepatocellular carcinoma (HCC) are still not clear. In the present work, our results demonstrate that MTBP could function as a co-activator of transcription factor E26 transformation-specific sequence (ETS-1), which plays an important role in HCC cell proliferation and/or metastasis and promotes proliferation of HCC cells. Using luciferase and real-time polymerase chain reaction (qPCR) assays, MTBP was found to enhance the transcription factor activation of ETS-1. The results from chromatin co-immunoprecipitation showed that MTBP enhanced the recruitment of ETS-1 to its downstream gene’s (mmp1’s) promoter region with ETS-1 binding sites. In cellular and nude mice models, overexpression of MTBP was shown to promote the proliferation of MHCC97-L cells with low endogenous MTBP levels, whereas the knockdown of MTBP led to inhibition of the proliferation of MHCC97-H cells that possessed high endogenous levels of MTBP. The effect of MTBP on ETS-1 was confirmed in the clinical specimens; the expression of MTBP was positively correlated with the downstream genes of ETS-1, mmp3, mmp9, and uPA. Therefore, by establishing the role of MTBP as a novel co-activator of ETS-1, this work expands our knowledge of MTBP or ETS-1 and helps to provide new ideas concerning HCC-related research.

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Section: Discussionmentioning

confidence: 99%

“…The role of ETS-1 in HCC has been widely reported ( 88 , 89 ). It is worth mentioning that the inhibitor of ETS-1 used in this study was ARQ-197, which is an inhibitor of c-MET ( 88 , 89 ). A report by Jie et al.…”

Section: Discussionmentioning

confidence: 99%