结直肠癌（CRC）转移是病人主要死亡原因。我们前期发现：电压门控钠通道SCN5A在CRC组织及细胞中高频高表达，且与CRC进展及不良预后显著正相关；外源性过表达SCN5A可促进CRC细胞上皮-间质转化和侵袭能力；而且发现二十二碳六烯酸（DHA）可下调CRC细胞中SCN5A并抑制其EMT和侵袭。本项目承前启后，拟在一系列体内外实验中并结合临床1）明确DHA通过调控PPRP下调SCN5A 抑制CRC细胞的确切分子通路与机制；2）阐明SCN5A通过上调Na+/H+交换体(NHE-1)促进CRC细胞EMT增强肿瘤转移的分子机理；3）最后在CRC裸鼠肝转移模型中确证DHA在通过下调SCN5A及其联合化疗有效抑制肿瘤转移的效果和新作用靶点；深入阐明DHA调控SCN5A在抑制CRC侵袭转移中的作用以及SCN5A促进CRC侵袭转移的详尽分子机制，为揭示CRC转移机制和抗肿瘤治疗策略提供实验研究基础和新线索

Metastasis is the main cause of patient death in patients with colorectal carcinoma (CRC). Our recent studies have found that voltage-gated sodium channels (SCN5A) was frequently overexpressed in CRC tissue and cell lines; SCN5A overexpression was positively correlated with the tumor progression and/or poor prognosis; In in vitro experiment, exogenous overexpression of SCN5A significantly induced CRC cells epithelial mesenchymal-transition(EMT) and enhanced their invasion and metastasis; Further study found docosahexaenoic acid (DHA) down-regulated SCN5A in CRC cells and inhibited their EMT and invasion. In the present project, a series of in vivo and in vitro experiments will be used to investigate the following issues by combining with CRC clinical samples,: 1) to indentify effects of DHA on inhibiting SCN5A expression in CRC cell lines and its associated molecular signaling pathway and mechanisms; 2) to elucidate the molecular mechanisms of SCN5A in promoting CRC cells EMT, invasion and metastasis through up-regulating Na+/H+ Exchanger-1(NHE-1); 3) finally, to verify that DHA inhibit CRC cell invasion and metastasis abilities through regulating SCN5A expression. These studies, taken together, will discover the effect of DHA in regulating SCN5A expression to promote CRC invasion, as well as its specific molecular mechanisms. Our study may provide better experimental basis and novel clues for further revealing the molecular mechanisms of CRC metastasis and potential strategies of anti-cancer treatment.