2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/642681摘要：胃癌是全球第四常見的惡性腫瘤。胃癌的惡性度與其生長、轉移、侵犯的能力息息相關。醣結構影響細胞的黏附及細胞間對話，且催化醣基化的酵素和腫瘤的生成與進展有關。O-醣化作用是生物界常見的轉譯後修飾，由N-乙酸氨基半乳糖轉移酶（N-acetylgalactosaminyltransferases，GALNT)酵素將醣基轉移到絲氨酸（serine）或羥丁氨酸（threonine）基上以形成短鍊的醣蛋白。研究顯示，剔除第二型 GALNT 的表現可以調控腫瘤行為。此研究的目的在於探討醣化相關生物反應在胃癌進展的作用。 首先，以免疫組織染色及西方墨點分析評估第二型 GALNT 在不同期的腸型胃癌中的表現，其結果再與臨床病理參數對照。初步結果即顯示，在晚期胃癌的組織中，第二型 GALNT 的表現較少。第二，剔除胃癌細胞株中第二型 GALNT 的表現，觀察比較其生物行為。初步結果即顯示有效剔除第二型 GALNT 後，AGS 細胞株生長、轉移、侵犯的能力增加。第三，建立胃癌的小鼠轉移模式，並使用非侵入式活體分子影像系統（IVIS）評估剔除第二型 GALNT胃癌細胞株的轉移能力。再者，以酪胺酸激酶受體陣列找尋第二型 GALNT的作用物，探討第二型 GALNT是否透過影響肝細胞生長因子受體 （c-Met） 活性而調控胃癌的進展。吾人的計畫可增進對於醣化作用在胃癌進展的了解，並有助於設計新療法。<br> Abstract: Gastric cancer (GC) is the fourth most prevalent cancers worldwide. Themalignant potential of GC correlates with their growth and metastatic ability.Glycan structures contribute to adhesion and intercellular communication, andenzymes regulating cellular glycosylation are related to the tumorigenesis.O-glycosylation is a common post-translational modification, which is initiatedby N-acetylgalactosaminyltransferases (GALNT) to transfer sugars to serine orthreonine residue to form short glycoprotein. Studies have shown thatGALNT2 knockdown could modify tumor behaviors. The aim of this proposal isto investigate GC progression in the view of glycobiology. First, we use IHC andwestern blot to evaluate the expression of GALTNT2 in the surgical specimenof intestinal type of GC, the result will be correlated with clinicopathologicalparameters. The preliminary data showed decreased GALNT2 expression inadvanced GC. Second, we would knockdown GALTNT2 in GC cell lines andobserve their phenotype changes. The preliminary data showedeffectively-knockdown AGS cells showed increased invasion, migration andproliferation. Third, we establish an in vivo metastasis model of GC, and useIVIs system to evaluate the metastasis potentials of GALNT2-knockdown AGS cells in mice. Forth, we would explore the substrate of GALTNT2 throughwhich modulating the progression of gastric cancers, and the preliminary RTKarray showed c-Met activity was increased by GALNT2 knockdown. Our studywould help understanding the roles of GALNT in gastric cancer progression andhelp designing novel therapies.