Zyxin (ZYX) promotes invasion and acts as a biomarker for aggressive phenotypes of human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYX expression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYX and demonstrated the role of ZYX in GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYX revealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1 were positively regulated by ZYX. Functionally, STMN1 not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYX loss. Taken together, our results indicate that high ZYX expression was associated with worse prognosis and highlighted that the ZYX-STMN1 axis might be a potential therapeutic target for GBM.

Deacetylation of chitin oligomers increases virulence in soil-borne fungal pathogens.

Soil-borne fungal pathogens that cause crop disease are major threats to agriculture worldwide. Here, we identified a secretory polysaccharide deacetylase (PDA1) from the soil-borne fungus Verticillium dahliae, the most notorious plant pathogen of the Verticillium genus, that facilitates virulence through direct deacetylation of chitin oligomers whose N-acetyl group contributes to host lysine motif (LysM)-containing receptor perception for ligand-triggered immunity. Polysaccharide deacetylases are widely present in fungi, bacteria, insects and marine invertebrates and have been reported to possess diverse functions in developmental processes rather than virulence. A phylogenetics analysis of more than 5,000 fungal proteins with conserved polysaccharide deacetylase domains showed that the V. dahliae PDA1-containing subtree includes a large number of proteins from the Verticillium genus as well as the Fusarium genus, another group of characterized soil-borne fungal pathogens, suggesting that soil-borne fungal pathogens have adopted chitin deacetylation as a major virulence strategy. We showed that a Fusarium PDA1 is required for virulence in cotton plants. This study reveals a substantial virulence function role of polysaccharide deacetylases in pathogenic fungi and demonstrates a subtle mechanism whereby deacetylation of chitin oligomers converts them to ligand-inactive chitosan, representing a common strategy of preventing chitin-triggered host immunity by soil-borne fungal pathogens.

Overexpression of ABCB4 contributes to acquired doxorubicin resistance in breast cancer cells in vitro.

PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry. In Madin-Darby Canine Kidney (MDCKII) cells, In vitro transport assay was used to assess the ABCB4-mediated transport of doxorubicin. RESULTS: ABCB4 was overexpressed in doxorubicin-resistant breast cancer cells compared to their doxorubicin-sensitive counterparts, which was associated with reduced DNA methylation as well as increased histone acetylation at the ABCB4 promoter. ABCB4 could actively pump doxorubicin out of the cells, and knockdown of ABCB4 increased doxorubicin sensitivity and intracellular accumulation in doxorubicin-resistant breast cancer cells. CONCLUSIONS: Our results indicate that ABCB4 is overexpressed in breast cancer cells with acquired doxorubicin resistance, which could be attributed, at least partially, to the epigenetic modifications of ABCB4 gene. ABCB4 mediates the efflux transport of doxorubicin, and contributes to the acquired resistance of doxorubicin in breast cancer cells.