Investigation of anti-tumor effects of an MLK1 inhibitor in prostate and pancreatic cancers

Yu Ching Fan, Kai Chen Hsu, Tony Eight Lin, Dietmar Zechner, Sung Po Hsu, Yuan Chin Tsai

研究成果: 雜誌貢獻文章同行評審

摘要

It was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the compound library of the National Cancer Institute (NCI) using a MLK1 protein structure. The inhibitory effects of MLK1 were validated by an in vitro kinase assay and by monitoring phosphorylation signaling, and the anti-proliferation function was shown in several prostate and pancreatic cancer cell lines. We also demonstrated anti-tumor ability and prevention of cancer-related weight loss in a syngeneic orthotopic mouse model of pancreatic cancer that mim-icked the tumor growth environment in the pancreas. Our results demonstrate that the MLK1 in-hibitor is an anti-tumor agent for malignant prostate and pancreatic cancers.

原文英語
文章編號742
期刊Biology
10
發行號8
DOIs
出版狀態已發佈 - 八月 2021

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 免疫學與微生物學 (全部)
  • 農業與生物科學 (全部)

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