上皮-間質轉化（epithelial mesenchymal transitions，EMT）是指上皮細胞在形態學上發生向成纖維細胞或間充質細胞表型的轉變並獲得遷移的能力。EMT是胚胎發育中的一個基本過程，它使在特殊部位產生的上皮細胞從上皮組織分離並遷移到其他位置，是正常發育、傷口癒合以及惡性上皮腫瘤發生的基礎。
腫瘤浸潤和轉移是癌症死亡的最常見的原因。上皮型腫瘤細胞侵入周圍組發生轉移，其中上皮間質轉化是必需的。近日，發表在PLoS On雜誌上的一則研究證明FGFR1在膀胱癌中的表達是增加的，FGFR1的激活誘導上皮癌（UC）細胞株發生EMT。
研究人員在體外創建了FGFR1誘導的EMT模型，並用這個模型來研究尿路上皮腫瘤的EMT過程。FGFR1的激活促進了72小時內的EMT。最初肌動蛋白應力纖維出現快速增長，細胞大小增加，腫瘤細胞形態發生改變，遷移和侵襲增加。
通過定點突變和小分子抑制劑證明，有絲分裂原活化蛋白激酶（MAPK）和磷脂酶C伽瑪（PLCγ）途徑調節EMT過程。肌動蛋白應力纖維的形成受PLCγ激活，對細胞大小增加，遷移和改變形態非常重要。MAPK的活化調控遷移和E-cadherin表達，表明PLCγ和MAPK的聯合激活對一個完整的EMT是需要的。
接下來，研究者採用晶片微列陳評估這些信號級聯的下遊基因表達的變化。發現FGFR1上調COX-2，造成細胞內前列腺素E（2）水平的增加，促進遷移。總之，研究數據證明，在上皮癌（UC）細胞株中，FGFR1的激活通過協調多個信號通路的激活，促進前列腺素合成激活，促進EMT。（生物谷：Bioon.com）
FGFR1-Induced Epithelial to Mesenchymal Transition through MAPK/PLCγ/COX-2-Mediated Mechanisms
Darren C. Tomlinson,1 Euan W. Baxter,1 Paul M. Loadman,2 Mark A. Hull,3 and Margaret A. Knowles1,*
Tumour invasion and metastasis is the most common cause of death from cancer. For epithelial cells to invade surrounding tissues and metastasise, an epithelial-mesenchymal transition (EMT) is required. We have demonstrated that FGFR1 expression is increased in bladder cancer and that activation of FGFR1 induces an EMT in urothelial carcinoma (UC) cell lines. Here, we created an in vitro FGFR1-inducible model of EMT, and used this model to identify regulators of urothelial EMT. FGFR1 activation promoted EMT over a period of 72 hours. Initially a rapid increase in actin stress fibres occurred, followed by an increase in cell size, altered morphology and increased migration and invasion. By using site-directed mutagenesis and small molecule inhibitors we demonstrated that combined activation of the mitogen activated protein kinase (MAPK) and phospholipase C gamma (PLCγ) pathways regulated this EMT. Actin stress fibre formation was regulated by PLCγ activation, and was also important for the increase in cell size, migration and altered morphology. MAPK activation regulated migration and E-cadherin expression, indicating that combined activation of PLCγand MAPK is required for a full EMT. We used expression microarrays to assess changes in gene expression downstream of these signalling cascades. COX-2 was transcriptionally upregulated by FGFR1 and caused increased intracellular prostaglandin E2 levels, which promoted migration. In conclusion, we have demonstrated that FGFR1 activation in UC cells lines promotes EMT via coordinated activation of multiple signalling pathways and by promoting activation of prostaglandin synthesis.