Katoh Masaru
Genetics and Cell Biology Section, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Mol Med. 2005 Dec;16(6):1103-8.
We cloned and characterized human WNT2B (WNT13) in 1996. Following our discovery of human WNT2B, others and we characterized mouse, rat, chicken and zebrafish WNT2B orthologs. Here, comparative integromics analyses on WNT2B and its clinical applications are reviewed. WNT2B-ST7L-CAPZA1 locus at human chromosome 1p13.2 and WNT2-ST7-CAPZA2 locus at human chromosome 7q31.2 are paralogous regions within the human genome. Two splicing variants occur from human WNT2B gene due to alternative promoters. WNT2B splicing variant 1 encodes secreted-type glycoprotein with WNT domain (WNT2B isoform 1), while WNT2B splicing variant 2 encodes transmembrane-type glycoprotein with WNT domain (WNT2B isoform 2). WNT2B splicing variant 2 is the evolutionarily conserved major transcript of human WNT2B gene. Mammalian WNT2B orthologs acquired the transmembrane domain and integrin-targeting RGD motif during vertebrate evolution. Human WNT2B isoform 2 and other vertebrate WNT2B orthologs are canonical WNTs to determine cell fate through the activation of beta-catenin/TCF signaling pathway and SNAIL/EMT signaling pathway. E box and CCAAT box are conserved within mammalian WNT2B promoters. WNT2B functions as the stem cell factor for neural or retinal progenitor cells during embryogenesis, and also for gastric cancer, esophageal cancer and skin basal cell carcinoma during carcinogenesis. Anti-WNT2B monoclonal antibody could be applied as selection marker of stem cells in the field of stem cell biology. Soluble WNT2B protein or small molecule WNT2B mimic compounds could be developed for stem cell expansion in the fields of tissue engineering and regenerative medicine. Anti-WNT2B monoclonal antibodies, WNT2B RNAi compounds, or small molecule WNT2B inhibitors could be developed as novel therapeutic agents for gastric cancer and esophageal cancer in the field of clinical oncology.
1996年，我们克隆并鉴定了人类WNT2B（WNT13）。在我们发现人类WNT2B之后，我们和其他研究人员对小鼠、大鼠、鸡和斑马鱼的WNT2B直系同源基因进行了鉴定。在此，对WNT2B的比较整合组学分析及其临床应用进行综述。人类染色体1p13.2上的WNT2B-ST7L-CAPZA1基因座和人类染色体7q31.2上的WNT2-ST7-CAPZA2基因座是人类基因组中的旁系同源区域。由于启动子的选择性使用，人类WNT2B基因产生两种剪接变体。WNT2B剪接变体1编码具有WNT结构域的分泌型糖蛋白（WNT2B亚型1），而WNT2B剪接变体2编码具有WNT结构域的跨膜型糖蛋白（WNT2B亚型2）。WNT2B剪接变体2是人类WNT2B基因在进化上保守的主要转录本。在脊椎动物进化过程中，哺乳动物的WNT2B直系同源基因获得了跨膜结构域和整合素靶向RGD基序。人类WNT2B亚型2和其他脊椎动物的WNT2B直系同源基因是经典的WNT，通过激活β-连环蛋白/TCF信号通路和SNAIL/EMT信号通路来决定细胞命运。E盒和CCAAT盒在哺乳动物WNT2B启动子中是保守的。WNT2B在胚胎发育过程中作为神经或视网膜祖细胞的干细胞因子发挥作用，在肿瘤发生过程中也作为胃癌、食管癌和皮肤基底细胞癌的干细胞因子发挥作用。抗WNT2B单克隆抗体可作为干细胞生物学领域中干细胞的选择标记。可溶性WNT2B蛋白或小分子WNT2B模拟化合物可用于组织工程和再生医学领域的干细胞扩增。抗WNT2B单克隆抗体、WNT2B RNAi化合物或小分子WNT2B抑制剂可作为临床肿瘤学领域中胃癌和食管癌的新型治疗药物开发。
