A non-tight junction function of claudin-7—Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment

Background Claudins are a family of tight junction (TJ) membrane proteins involved in a broad spectrum of human diseases including cancer. Claudin-7 is a unique TJ membrane protein in that it has a strong basolateral membrane distribution in epithelial cells and in tissues. Therefore, this study aims to investigate the functional significance of this non-TJ localization of claudin-7 in human lung cancer cells. Methods Claudin-7 expression was suppressed or deleted by lentivirus shRNA or by targeted-gene deletion. Cell cycle analysis and antibody blocking methods were employed to assay cell proliferation and cell attachment, respectively. Electron microscopy and transepthelial electrical resistance measurement were performed to examine the TJ ultrastructure and barrier function. Co-immunolocalization and co-immunoprecipitation was used to study claudin-7 interaction with integrin β1. Tumor growth in vivo were analyzed using athymic nude mice. Results Claudin-7 co-localizes and forms a stable complex with integrin β1. Both suppressing claudin-7 expression by lentivirus shRNA in human lung cancer cells (KD cells) and deletion of claudin-7 in mouse lungs lead to the reduction in integrin β1 and phospho-FAK levels. Suppressing claudin-7 expression increases cell growth and cell cycle progression. More significantly, claudin-7 KD cells have severe defects in cell-matrix interactions and adhere poorly to culture plates with a remarkably reduced integrin β1 expression. When cultured on uncoated glass coverslips, claudin-7 KD cells grow on top of each other and form spheroids while the control cells adhere well and grow as a monolayer. Reintroducing claudin-7 reduces cell proliferation, upregulates integrin β1 expression and increases cell-matrix adhesion. Integrin β1 transfection partially rescues the cell attachment defect. When inoculated into nude mice, claudin-7 KD cells produced significantly larger tumors than control cells. Conclusion In this study, we identified a previously unrecognized function of claudin-7 in regulating cell proliferation and maintaining epithelial cell attachment through engaging integrin β1

HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells

The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX2 to four different CDX2 binding sites in an enhancer region located upstream of the HOXB4 transcription start site. Mutations in the CDX2 binding sites reduced HOXB4 gene activity, and knock down of endogenous CDX2 expression by shRNA reduced HOXB4 gene expression. This is the first report demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis

CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing’s sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone

المواد المتطايرة من الطحلب البني هور موفيسا كينوفورميس الذي ينمو على السواحل القطرية

The present work deals with the study on volatile compounds from the brown alga Hormophysa cuneiformis collected from the Northwest coast of Qatar on May 2002. Two extraction methods have been used: conventional hydrodistillation of the crude diethyl ether extract of alga and supercritical CO2 extraction of the same crude extract with two different stationary phases for the trapping. The obtained oils were examined by GC/MS coupling experiments and the chemical compositions obtained from both methods were compared. Their major constituents were: squalene described for the first time from a macroalga, fatty acids and corresponding esters. It must be pointed out absence of volatile C-l 1 hydrocarbons which are commonly presents in brown algae might be due to the collecting period of the alga (May) which probably favors the metabolism of unsaturated fatty acids precursors of these C-l 1 hydrocarbons. The presence, in a small amount, of a C-l 1 sulphur compound with a near related biogenesis of the volatile C-ll hydrocarbons is in agreement with this hypothesis.تمت دراسة المواد المتطايرة من الطحلب البني هورموفيسا كينوفورميس المجموع من شواطئ قطر في مايو 2002 وذلك باستخدام طريقتين للاستخلاص وهما الطريقة التقليدية لاستخلاص ( التقطير البخاري) لمستخلص الايثر والاستخلاص باستخدام ثاني أكسيد الكربون. وأظهرت الدراسة باستخدام كروماتوجرافيا الغاز وطيف الكتلة أن المكونات الأساسية للزيت الطيار هي الأحماض الدهنية والاسترات المشتقة منها وقلة وجود C-11 هيدروكربونات متطايرة. وربما يكون ذلك بسبب الفترة التي تم فيها جمع الطحلب والتي تكون مناسبة لأيض الأحماض الدهنية غير المشبعة التي تتكون منها هذه الهيدروكربونات ويؤيد هذا الافتراض وجود كميات قليلة من C-11 هيدروكربونات كبريتية