食道癌是全球第八大癌症也是癌症相關死亡率的第六大起因，估計每年全球有45.6萬新發病例。食道癌平均5年存活率僅為15％，同時在原發腫瘤切除後，其復發率高達4成。在台灣，雖然食道癌是國人第九大癌症死因，但近幾年，食道癌發病率有逐年攀升的現象。Hippo pathway其主要功能為調控細胞增生，存活，幹細胞分化和器官大小的關鍵途徑。而YAP 和其旁系同源物TAZ是Hippo pathway 的主要轉錄共調因子，在不同癌症類型中，Hippo pathway 的下游調控因子YAP和TAZ經常被描述為具有相同功能，但是近年來的研究發現在癌症進展期間，不同基因的表達譜的YAP或TAZ，可能扮演不同的角色。在數種癌症類型中發現Hippo pathway有失活現象，然而在食道癌中，Hippo pathway 和其下游YAP和TAZ的確切作用仍然不清楚。因此在這論文中，我們分別討論YAP或TAZ在食道癌進程中所扮演的角色。首先我們利用西方墨點法檢測各種食道癌細胞株YAP / TAZ的差異表達。透過基因的靜默或過量表達，我們意外地發現在食道癌中，YAP和TAZ對於體外細胞增生，遷移和侵襲甚至動物體內腫瘤的形成具有相反的功能。儘管YAP和TAZ在食道癌中扮演不儘相同甚至相反的角色與機制仍值得進一步研究，此研究結果將有助於證實Hippo pathway及其作用因子YAP / TAZ在食道癌中的確切作用。

Esophageal cancer is the 8th most common cancer and the 6th leading cause of cancer-related mortality in the world, with an estimated 456,000 new cases per year worldwide. In addition to high recurrence rate (~40%) even after resection of the primary tumor, the 5-year survival rate for all stages of esophageal cancer is only 15%. Although esophageal cancer is the ninth cause of cancer death in Taiwan, the incidence rate is on the rise especially in the past few years. Hippo pathway has been shown to be a key pathway involved in cell proliferation, survival, stemness, differentiation and organ size control. The transcription co-regulators, YAP and its paralog, TAZ, are the central mediators for Hippo pathway. Although YAP and TAZ have often been described to be the equivalent downstream effectors of the Hippo pathway in different cancer types, differential expression profiles of YAP or TAZ suggest distinct roles during cancer progression. Although more and more studies detected the inactivation of Hippo pathway in several cancer types, the exact role of Hippo pathway and its downstream mediators, YAP and TAZ, in esophageal cancer remains to be characterized. To examine the role of YAP/TAZ in esophageal cancer, we first detected a differential expression of YAP/TAZ in various esophageal cancer lines. Through genetic silencing and overexpression, we unexpectedly found that YAP and TAZ have opposing functions in mediating esophageal cancer cell proliferation, migration and invasion as well as xenograft tumorigenesis. Although the contrasting role of YAP and TAZ deregulation in esophageal cancer warrants further mechanistic studies, this study results would help corroborate the exact role of Hippo pathway and its effectors, YAP/TAZ, in esophageal cancer.

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