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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer
Scientific Reports, Volume 6, Article 33121, Year 2016
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Description
Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer. © The Author(s) 2016.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC5020615/bin/srep33121-s1.pdf
Authors & Co-Authors
Csizmadia, Eva
United States, Boston
Beth Israel Deaconess Medical Center
Miksad, Rebecca Anne
United States, Boston
Beth Israel Deaconess Medical Center
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Statistics
Citations: 26
Authors: 3
Affiliations: 4
Identifiers
Doi:
10.1038/srep33121
ISSN:
20452322
Research Areas
Cancer
Study Design
Randomised Control Trial
Cohort Study