b-catenin is a multifunctional protein identified to be pivotal in embryonic patterning, organogenesis and adult homeostasis. It plays a critical structural role in mediating cadherin junctions and is also an essential transcriptional co-activator in the canonical Wnt pathway. Evidence has been documented that both the canonical Wnt pathway and cadherin junctions are deregulated or impaired in a plethora of human malignancies. In the light of this, there has been a recent surge in elucidating the mechanisms underlying the etiology of cancer development from the perspective of b-catenin. Here, we focus on the emerging roles of b-catenin in the process of tumorigenesis by discussing novel functions of old players and new proteins, mechanisms identified to mediate or interact with b-catenin and the most recently unraveled clinical implications of b-catenin regulatory pathways toward tumor suppression.Since its identification as an essential and central component in the Wnt signaling cascade, and the subsequent finding of its pivotal role in cadherin-based cell-cell adhesion, b-catenin has been critically studied to elucidate the coordination of these two pathways. The significance of this coordination is substantiated in a plethora of metabolic processes, such as axis and mesoderm formation, stem cell differentiation and carcinogenesis. 1,2 Generally, the Wnt pathway is divided into four branches, namely the canonical Wnt/b-catenin pathway, and the noncanonical (or heretical) Wnt/Ca 2þ and planar cell polarity pathways. Amongst them, the canonical Wnt pathway is the best studied and is reported to be highly conserved through evolution but is frequently altered in many human malignancies such as colorectal cancers, hepatocellular carcinomas and gastric cancers. 3-6 Ca 2þ -dependent cellcell adhesion in the cadherin family of proteins is typified by an extracellular segment that consists of five distinct Ca 2þ -binding domains and a conserved cytoplasmic domain, which interacts with b-catenin and p120 catenin (herein p120); b-catenin then provides a binding site for a-catenin. Cadherin junctions, among other cell-cell adhesion complexes, are essential for cellular processes such as cell polarity and migration. 7,8 Since an indispensible morphological hallmark of malignant tumors is reduced cell-cell adhesiveness, it is predicted that the components of cadherin junctions in many human malignancies, such as breast cancer, colorectal cancer and prostate cancer, are genetically altered. 9-11 Besides cellcell adhesion, cadherin junctions function as a potent competitor of free cytosolic b-catenin. This is supported by studies of the co-crystal structures of b-catenin/cadherin and b-catenin/TCF revealing that the two b-catenin ligands shared overlapping binding regions along b-catenin. 12 The role of the cadherin junction in the subcellular distribution of b-catenin has recently been further extended as discussed below.In this review, a myriad of recently emerged mechanisms governing the signaling and adhesive activity of ...

The aim of the present study was to investigate the antibiotic resistance profiles and the molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from two production swine operations in Sichuan Province, China, between August 2002 and February 2007. The prevalence of ESBL-producing E. coli increased dramatically from 2.2% to 10.7% during this period. This increase appeared mostly related to dissemination of CTX-M-type ESBLs among E. coli isolates. Of 212 E. coli isolates studied, 14 harbored ESBL genes. Among them, 13 harbored bla(CTX-M-15/22) and one harbored bla(SHV-2). To our knowledge, this is the first study to identify bla(CTX-M-22) from production animals. One isolate in 2002 harbored bla(SHV-2), indicating that ESBL genes have been present in farm animals in China since at least 2002. Molecular characterization and pulsed-field gel electrophoresis of the ESBL-producing isolates suggested that different mechanisms may be involved in the dissemination of the CTX-M genes and revealed that additional resistance determinants for non-beta-lactam antibiotics were carried by plasmids encoding certain ESBL genes. Results of this study provide an example of how ESBL genes, particularly those of CTX-M lineages, are rapidly spreading among E. coli isolates from commercial pig farms in Sichuan province of China.

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The investigation and development of the cancer stem cell (CSC) model has received much focus during these years. CSC is characterized as a small fraction of cancer cells that have an indefinite ability for self-renewal and pluripotency and are responsible for initiating and sustaining of the bulk of cancer.

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The significance of BmK CT, a key chlorotoxin-like peptide isolated from the scorpion venom of Buthus martensii Karsch, is a novel blocker of the chloride ion channel and matrix metalloproteinase-2 (MMP-2). Site-directed mutagenesis of BmK CT, wound healing assay, gelatin zymography assay and computational simulation highlight the importance of electrostatic contribution to BmK CT-MMP-2 catalytic domain complex and a model of BmK CT-MMP-2 catalytic domain complex is therefore proposed. This is the first documentation of the structural mechanism of in the inhibition of glioma cell migration by BmK CT and may lead to the molecular design of specific inhibitors of MMP-2.