Abstract
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.
Original language | English |
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Article number | 742 |
Journal | Biology |
Volume | 10 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2021 |
Keywords
- Androgen receptor
- MLK1
- Pancreatic cancer
- Prostate cancer
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences