To dissect the multi-step genetic and epigenetic alterations involved in the pathogenic development of human gastrointestinal track tumors, we have performed various approaches of representational difference analyses and identified more than two thousands genes that are differentially expressed in gastric cancer (GC). A GC gene chip based on these genes was generated, and hybridized to cDNA probes derived from 50 GC patients with well-defined pathological features. By cluster analyses, critical genes and signaling pathways associated with GC were identified. The molecular mechanisms through which the deregulated genes and pathways contributing to the acquisition of various cancer hallmarks are dissected and recapitulated in cell culture and animal studies. The topics studied at the present time in the laboratory are focused on the roles of osteopontin/CD44-mediated signaling in shaping the tumor microenvironment, suppressor of cytokine signaling 6 (socs6) in regulating mitochondrial function and apoptosis, and Rho effector Rhotekin in regulating cell movement and survival. The goals of our studies are to provide an in-depth understanding of the molecular mechanisms underlying the pathogenic development and progression of GC, with the hope to establish better choices of markers for diagnosis and treatment, and in the long run, to provide the common denominator for understanding, treating, and preventing this disease.
為了進一步瞭解腸胃道腫瘤發生、進展及惡化的機制，我們利用代表性差異展示法，分離出兩千多種在胃癌組織呈現差異表現性的基因，將其製成胃癌晶片，利用cDNA微陣列及群組分析，確認與胃癌病變有密切關連的基因及訊息傳遞路徑，進而探討其參與調控細胞增生、存活與遷移的分子機制，並以動物模式來瞭解其在癌症病變及轉移中所扮演的角色；目前我們深入研究的主體包含Osteopontin/CD44訊息傳遞調控腫瘤與其周遭環境互動的機制，Suppressor of cytokine signaling 6 (SOCS6) 對粒線體功能及細胞凋亡的影響，及Rho 的交互蛋白 Rhotekin對細胞移動及存活的調控；我們希望這些研究能讓我們更了解癌症致病及惡化的機轉，並提供癌症病患較佳的診斷及預後的標誌，最終極的目的是希望能促進我們瞭解、治療及預防癌症的方針。