口腔鱗狀上皮細胞癌屬於頭頸癌中最普遍且惡性的腫瘤之一，在台灣則好發於男性。癌症轉移是一個漸進的過程，癌細胞會從原位轉移到遠端，然而癌症的轉移也代表著不好的預後和高死亡率。有許多台灣病患被診斷出口腔癌時都已經是晚期了，這意味著口腔癌早已發生轉移。因此，我們主要是想從口腔癌中找出具有轉移專一的生物標誌分子，並且對於標的蛋白在口腔癌轉移的角色，提供全面的功能性了解。分泌蛋白的不正常分泌表現，可能對於癌症轉移是一個病理上的指標。有越來越多的分泌蛋白被報導，透過與腫瘤微環境的調控參與癌症的轉移，且那些分泌蛋白對於預防癌症轉移被認為是潛在的標的。在差異性二微電泳(2D-DIGE)和基質輔助雷射脫附游離飛行時間式質譜儀(MALDI-TOF MS)的配合之下，分泌蛋白質體學的分析提供一個平台來找到有潛力的標的。我們鑑定出一群差異性表現的分泌蛋白，這些分泌蛋白的差異性表現調控著口腔癌的轉移。在這些潛力蛋白之中，半乳糖凝集素-1(LGALS1)被發現在具有高度侵略性口腔癌細胞中大量表現。我們利用核糖核酸干擾的技術來探討半乳糖凝集素-1在口腔癌轉移中的作用與角色。從我們的實驗結果中顯示，減弱半乳糖凝集素-1的表現會顯著的降低口腔癌細胞的增生並誘導細胞停留在去氧核醣核酸的合成期。另外，減弱半乳糖凝集素-1的表現也會抑制口腔癌細胞的移動和入侵能力。我們在高度侵略性口腔癌細胞中發現，p38 MAPK激酶調控的基質金屬蛋白酶-9的訊息傳遞路徑有活化的現象跟細胞呈現間質的表現型，然而減弱半乳糖凝集素-1的表現會降低p38 MAPK激酶的磷酸化、減少基質金屬蛋白酶-9的表現、減低調控上皮細胞間質轉化的轉錄因子的表現。總而言之，我們認為半乳糖凝集素-1的確参與調控口腔癌細胞的轉移特性。我們的研究成果也指出高表現的半乳糖凝集素-1和口腔癌的發展及轉移有著很大的關係，因此，半乳糖凝集素-1可望成為診斷口腔癌預後具有潛力的生物標誌分子及治療口腔癌的新穎標的。

Oral squamous cell carcinoma (OSCC), one of the most prevalent malignant tumors among head and neck cancers, predominantly takes place in males in Taiwan. Metastasis is a progressive process that promotes the dissemination of cancer cells from the primary tumor to distant sites and responsible for poor prognosis and high mortality. In Taiwan, most patients were diagnosed with oral cancer in advanced stage, which means metastatic oral cancer is occurred. Here, we aimed to evaluate metastasis-specific markers in oral cancer and to provide comprehensive recognition concerning functional roles of the specific target in oral cancer metastasis. An irregulated expression of secreted proteins might be an indicator for pathological index of cancer metastasis. More and more secreted proteins have been reported to be involved in cancer metastasis through modulation of the tumor microenvironment, and those secreted proteins also suggest to be the potential targets for preventing cancer metastasis. Secretomic analysis based on two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) provides a platform for potential target discovery. A group of differentially expressed proteins were identified and showed their biological characteristics in mediating oral cancer metastasis. Among the potential proteins, lectin, galactoside-binding, soluble, 1 (LGALS1) was observed to be upregulated in highly invasive oral cancer cells. RNA interference technique was performed to investigate the role of LGALS1 in oral cancer metastasis. Our data showed that knockdown of LGALS1 significantly reduced cell proliferation and induced S phase arrest. Silencing LGALS1 resulted in the inhibition of oral cell migration and invasion. Activation of the p38 MAPK-mediated MMP-9 pathway and mesenchymal phenotypes of EMT were observed in highly invasive oral cancer cells, whereas downregulated LGALS1 decreased the phosphorylation of p38 MAPK, MMP-9 expression, and the expression of EMT-regulating transcription factors. Collectively, we propose that secreted LGALS1 is involved in the metastatic potential of oral cancer cells. These findings demonstrate that elevated LGALS1 is strongly correlated with oral cancer progression and metastasis, and that it could potentially serve as a prognostic biomarker and an innovative target for oral cancer therapy.

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