上呼吸消化道癌是世界上第三大的癌症類型，範圍囊括口腔、鼻腔、咽、喉、氣管與食道，其中食道癌與口腔癌分別為上呼吸消化道癌的兩大主要類型。致病因子為吸菸、酗酒、嚼食檳榔與熱飲。病理分期於遠端器官轉移階段的罹病患者其五年存活率僅剩20-30%。然而目前對於上呼吸消化道癌進展與轉移之機制方面的研究仍保有很大的探討空間。本論文研究主要著重於研究The adhesion molecule with Ig like domain 2 (AMIGO2)，其為typeⅠ穿膜蛋白。於先前的文獻已提及AMIGO2參與胃致癌作用，並作為腫瘤血管生成所需的主要細胞類型—血管內皮細胞的存活因子之功用。但AMIGO2在上呼吸消化道癌的功能與作用機制仍未有深入的了解。透過查詢分析TCGA—食道癌與頭頸癌的資料庫數據，我們發現在上述癌症中AMIGO2表現量上升，而在頭頸癌中AMIGO2上升趨勢表現與預後不佳顯著相關。因此我們嘗試經由於體外實驗降低或過度表現AMIGO2以研究AMIGO2失調於上呼吸消化道癌所扮演的角色。經由驗證AMIGO2在不同上呼吸消化道癌細胞株的蛋白表現，我們進一步發現當改變AMIGO2的表現量時，AMIGO2會調控上呼吸消化道癌細胞株的增生、菌落形成、移動、侵入與不同基質蛋白下的細胞附著功能，同時我們也會探討AMIGO2在細胞附著所調控的訊息傳遞路徑與上皮間質轉化中的參與角色。最後透過此次研究，我們希望提供在上呼吸消化道癌中AMIGO2失調所扮演的角色與其作用機制。

Upper aerodigestive tract cancer (UATC) is the third leading cancer type in the world, including those in oral cavity, nasal cavity, pharynx, larynx, trachea and esophagus. Esophageal cancer and oral cancer are two major types of UATC. Furthermore, more than 90% of this cancer type is squamous cell carcinoma. Their major risk factors include smoking, alcohol consumption, chewing betel nut, and hot drinks. The 5-yr survival rates for these patients with distant metastasis stage is only 20-30%. In the year of 2018, oral cancer, a subtype of head and neck cancer, and esophageal cancer are, respectively, the 5th and 6th leading causes of male cancer death in Taiwan. However, the underlying mechanism for UATC progression and metastatic spread remains elusive. The adhesion molecule with Ig like domain 2 (AMIGO2) a type Ⅰ transmembrane protein. AMIGO2 was recently shown to participate in gastric carcinogenesis and function as a survival factor for vascular endothelial cells, the major cell type required for tumor angiogenesis. However, its function and action mechanism in UATC remains elusive. Through the exploration of TCGA-esophageal and head and neck cancer databases, we also found the up-regulation of AMIGO2 in these cancer subtypes and the up-regulation was significantly associated with poor prognosis among head and neck cancer patients. We then aimed to study the role of AMIGO2 deregulation in UATC cells by using knockdown or overexpression methods followed by in vitro models. Following the validation of differential AMIGO2 protein expression in these cancer cell lines, we further showed that altered AMIGO2 expression could modulate the proliferation, colony formation, cell migration, cell invasion and cell adhesion to various matrix proteins in context-dependent manners. The involvement of AMIGO2 in cell adhesion-mediated signaling pathways and EMT were also studied by Western blots. Through this study, we hope to provide a role for AMIGO2 deregulation and its actin mechanism in UATC.

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