Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC. METHODS: Correlation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo. RESULTS: PTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo. CONCLUSION: This study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.

Identification and characterization of odorant binding proteins in the diamondback moth, Plutella xylostella.

Odorant binding proteins (OBPs) are a group of soluble proteins functioning as odorant carriers in insect antennae, mouth parts and other chemosensory organs. However, multiple insect OBPs have been detected in other tissues and various functions have been proposed. Therefore, a detailed expression profile including stages, tissues and sexes where OBPs are expressed will assist in building the links to their potential functions, enhancing the functional studies of insect OBPs. Here, we identified 39 putative OBP genes from its genome and transcriptome sequences of diamondback moth (DBM), Plutella xylostella. The expression patterns of identified PxylOBPs were further investigated from eggs, larvae, pupae, virgin adults, mated adults, larval midgut, larval heads, adult antennae, adult heads and adult tarsi. Moreover, P. xylostella larvae and adults with and without host plants for 5 h were utilized to study the interactions between OBP expression and host plants. The results showed that most PxylOBPs were highly expressed in male and female adult antennae. The expression levels of certain PxyOBPs could be regulated by mating activities and feeding host plants. This study advances our knowledge of P. xylostella OBPs, which may help develop new strategies for more environmentally sustainable management of P. xylostella.

Altered Profiles of Gut Microbiota in Klebsiella pneumoniae-Induced Pyogenic Liver Abscess.

Intestinal microbiota plays a crucial role in preventing the colonization and invasion by pathogens, and disruption of microbiota may cause opportunistic infections and diseases. Pathogens often have strategies to escape from the colonization resistance mediated by microbiota, but whether they also modulate the microbiota composition is still a topic of investigation. In the present study, we addressed this question using an opportunistic pathogen, Klebsiella pneumoniae serotype K1, which is known to cause pyogenic liver abscess (KLA) in about 30% of mice. We examined the effect of K. pneumoniae infection on cecal microbiota composition by performing high-throughput 454 pyrosequencing of the hypervariable V3-V4 regions of bacterial 16S rRNA gene. Our data revealed that K. pneumoniae inoculation substantially changed the cecal microbiota composition when analyzed at the phylum, order, and family levels. Most strikingly, the KLA-infected mice had significantly increased abundance of Bacteroidales and Enterobacteriales and decreased abundance of Lactobacillales and Eggerthellales. Furthermore, by comparing the infected mice with or without KLA disease symptoms, we identified specific microbiota changes associated with the KLA disease induction. Especially, the KLA group had dramatically decreased sequence identical to Lactobacillus compared with non-KLA mice. These findings suggest that the pathogenic process of KLA infection may involve alteration of microbiota compositions, particularly reduction in Lactobacillus.

The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis.

Different domains of the multifunctional transcription factor Y-box binding protein 1 (YB1) regulate proliferation, differentiation, and apoptosis by transactivating or repressing the promoters of various genes. Here we report that the C-terminal domain of YB1 (YB1 CTD) is involved in endothelial cell proliferation, apoptosis, and tube formation. The oligo pull-down assays demonstrated that YB1 directly binds double-stranded GC box sequences in endothelial cells through the 125-220 amino acids. Adenovirus expression vectors harboring green fluorescent protein (GFP) or GFP-tagged YB1 CTD were constructed and used to infect EA.hy926 endothelial cells. Overexpression of the YB1 CTD significantly increased p21 expression, decreased cyclin B1 expression, and inhibited the proliferation of EA.hy926 cells. YB1 CTD overexpression also increased Bax and active caspase 3 expression, decreased Bcl-2 expression, and induced apoptosis in EA.hy926 cells. Furthermore, overexpression of the YB1 CTD significantly suppressed migration and tube formation in EA.hy926 cells. Finally, YB1 CTD decreased ERK1/2 phosphorylation in EA.hy926 cells. These findings demonstrated vital roles for YB1 in endothelial cell proliferation, apoptosis, and tube formation through transcriptional regulation of GC box-related genes.