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Báo cáo y học: " Roles of XB130, a novel adaptor protein, in cancer"

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Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Roles of XB130, a novel adaptor protein, in cancer. | Shiozaki and Liu Journal of Clinical Bioinformatics 2011 1 10 http www.jclinbioinformatics.eom content 1 1 10 JOURNAL OF CLINICAL BIOINFORMATICS REVIEW Open Access Roles of XB130 a novel adaptor protein in cancer Atsushi Shiozaki 1 Mingyao Liu2 3 Abstract Adaptor proteins with multi-modular structures can participate in the regulation of various cellular functions. During molecular cloning process of actin filament associated protein we have discovered a novel adaptor protein referred to as XB130. The human xb130 gene is localized on chromosome 10q25.3 and encodes an 818 amino acid protein. The N-terminal region of XB130 includes several tyrosine phosphorylation sites and a proline-rich sequence that might interact with Src homology 2 and 3 domain-containing proteins respectively. Our studies have indeed implicated XB130 as a likely substrate and regulator of tyrosine kinase-mediated signaling. Down-regulation of endogenous XB130 with small interfering RNA reduced c-Src activity IL-8 production and phosphorylation of Akt in human lung epithelial cells. Further XB130 binds the p85a subunit of phosphatidyl-inositol-3-kinase and subsequently mediates signaling through RET PTC in thyroid cancer cells. Knockdown of XB130 using small interfering RNA inhibited G1-S phase progression induced spontaneous apoptosis and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death in human lung and thyroid cancer cells. Growth of tumors in nude mice formed from XB130 short hairpin RNA stably transfected human thyroid cancer cells were significantly reduced with decreased cell proliferation and increased apoptosis. Further XB130 has a high affinity to lamellipodial F-actin meshwork and is involved in the motility and invasiveness of cancer cells. Gene expression profiling identified 246 genes significantly changed in XB130 short hairpin RNA transfected thyroid cancer cells. Among them 57 genes are related to cell proliferation or survival including many transcription

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