Project description:The goal of this study is to compare the different biological functions between nuclear (ICD)-TYRO3- and kinase dead (KD)-TYRO3-overexpressed cells by BRD3 occupancy profiling. We revel that ICD-TYRO3-overexpressed cell were particularly enriched in negatively regulate cell death, regulation of cell cycle, regulation of vascular permeability, positively regulation of EMT, cell-cell adhesion, and regulation of phosphorylation.
Project description:Colorectal cancer (CRC) is one of the most common death-related cancers worldwide. Aberrant expression of oncogenes is regarded as a predominant factor in CRC development. In our study, we found that TYRO3 intracellular domain nuclear translocation promotes CRC cell proliferation, metastasis, and tumor progression. To identify downstream effector that transmits the cellular functions of nuclear TYRO3, we performed nuclear TYRO3 co-immunoprecipitation.
Project description:Tyro3 is a member of the TAM (Tyro3, Axl and Mer) receptor family. In this study, we want to know potential association between Tyro3 expression in HCC and the involved signaling pathway.
Project description:The goals of this study are to compare transcriptome profiling among four different cell lines including parental cells, resistant cells, Tyro3-overexpression cells, and Tyro3 knockout cells.
Project description:To better understand the molecular mechanisms underlying TYRO3 oncogenic activity in bladder carcinomas, we made use of MGH-U3, RT112 and UM-UC-5 cell lines, which were derived from a human bladder tumor and endogenously expressed the Tyro3 protein, the growth and transformation of these cell lines being dependent on Tyro3. We carried out a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not withTYRO3 siRNAs.
Project description:Non-Hodgkin’s lymphomas (NHL) make up the majority of lymphoma diagnoses and represent a very diverse set of malignancies. We sought to identify kinases uniquely upregulated in different NHL subtypes. Using Multiplexed Inhibitor Bead-mass spectrometry (MIB/MS), we found Tyro3 was uniquely upregulated and important for cell survival in primary effusion lymphoma (PEL). We developed an inhibitor against Tyro3 named UNC3810A, which inhibited cell growth in PEL but not in other NHL subtypes. UNC3810A also significantly inhibited tumor progression in a PEL xenograft mouse model compared to the vehicle treated animals. Our data suggests Tyro3 may be a therapeutic target for PEL.
Project description:CDK8 Mediator kinase is amplified and overexpressed in colon cancers; elevated CDK8 expression is associated with shorter patient survival. Nevertheless, CDK8 kinase inhibitors do not generally suppress colon cancer growth. We addressed this paradox by investigating the effects of CDK8 knockdown or a CDK8 kinase inhibitor on tumor growth at primary and metastatic sites. CDK8 knockdown or inhibition had no significant effect on primary tumors but suppressed the growth of hepatic metastases in murine and human colon cancer models. The effect of CDK8 inhibition on liver metastasis is mediated by upregulation of matrix metalloproteinase (MMP) inhibitor TIMP3 and downregulation of several MMPs.
Project description:CDK8 Mediator kinase is amplified and overexpressed in colon cancers; elevated CDK8 expression is associated with shorter patient survival. Nevertheless, CDK8 kinase inhibitors do not generally suppress colon cancer growth. We addressed this paradox by investigating the effects of CDK8 knockdown or a CDK8 kinase inhibitor on tumor growth at primary and metastatic sites. CDK8 knockdown or inhibition had no significant effect on primary tumors but suppressed the growth of hepatic metastases in murine and human colon cancer models. The effect of CDK8 inhibition on liver metastasis is mediated by upregulation of matrix metalloproteinase (MMP) inhibitor TIMP3 and downregulation of several MMPs.