ASCT2介导的谷氨酰胺代谢在OPMD癌变中的作用研究

转运体ASCT2在多种肿瘤细胞谷氨酰胺的摄取、转运过程中发挥着主要作用，是肿瘤细胞代谢谷氨酰胺的关键环节之一。然而，ASCT2及其介导的谷氨酰胺代谢在口腔潜在恶性病变（OPMDs）恶化及随后的肿瘤侵袭与转移过程中的作用并未明确。申请人前期研究发现，ASCT2表达水平在正常组织、口腔潜在恶性病变口腔白斑（OLK）、口腔鳞癌（OSCC）组织中逐渐增高，同时靶向干扰ASCT2表达可有效抑制OSCC细胞谷氨酰胺代谢，从而抑制肿瘤细胞的生长与侵袭。据此，申请人做出如下科学假说：高表达的ASCT2介导了OLK组织谷氨酰胺的代谢增加，进而促进了OLK癌变以及随后的肿瘤侵袭与转移。因此，本项目拟利用小鼠模型与临床样本，从体内外研究ASCT2在OLK发生、癌变过程以及随后肿瘤侵袭与转移中的重要作用，从而探讨以ASCT2为靶点阻断OLK癌变、防治OSCC的有效性及可行性。

ASCT2, a new identified neutral amino acid exchanger, which is the major glutamine transporter in cancer cells. Previous studies have reported that the glutamine uptake mediated by ASCT2 is important for cancer cell growth in lung cancer, neuroblastoma, melanoma, head and neck cancer and prostate cancer. However, the role of ASCT2-mediated Glutaminolysis during the Carcinogenesis of Oral Leukoplakia has not been determined untill now. In our prious study, we observed that the increase of glutaminolysis mediated by higher ASCT2 may contributie to the carcinogenesis oral leukoplakia. Moreover, ASCT2 knock-down could significantly inhibit tumor growth and metastasis of OSCC. Therefore, this study was designed to determine the critical role of glutaminolysis mediated by ASCT2 in the malignant transformation of OLK and succedent invasion and metastasis of OSCC in Vitro and Vivo. It will help us to understand the validity and feasibility of ASCT2 to prevent the maliganant transformation of OLK and the invasion of OSCC.