UNASSIGNED: @entity3 causes most @entity5 related mortality but the mechanisms governing metastatic dissemination are poorly defined. @entity3 involves egression of @entity5 cells from the @entity5 , their survival in circulation and colonization at the secondary sites. Cancer cell egression from the @entity5 is the least defined process of @entity3 as experimental @entity3 models directly seed @entity5 cells in circulation, thus bypassing this crucial step. Here, we developed a spontaneous @entity3 model that retains the egression step of @entity3 . By repeated in vivo passaging of the poorly metastatic @entity2 (3LL) cells, we generated a cell line (p-3LL) that readily metastasizes to lungs and liver from subcutaneous (s.c.) @entity5 . Interestingly, when injected intravenously, 3LL and p-3LL cells showed a similar frequency of @entity3 . This suggests enhanced egression of p-3LL cells may underlie the enhanced metastatic spread from @entity5 . Microarray analysis of 3LL and p-3LL cells as well as the @entity5 derived from these cells revealed altered expression of several genes including significant upregulation of a tight junction protein, @entity69378 . Increased expression of @entity69378 was confirmed in both p-3LL cells and @entity5 derived from these cells. Knockdown of @entity69378 expression in p-3LL cells by si-RNA significantly reduced their motility, invasiveness in vitro and @entity3 in vivo. Conversely, transient overexpression of @entity69378 in 3LL cells enhanced their motility. These results suggest an essential role for @entity69378 in promoting @entity2 @entity3 .

A spontaneous @entity3 model reveals the significance of @entity69378 overexpression in @entity2 XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['primary tumors', 'cancer', 'primary tumor', 'tumors'] @entity69378 :: ('9080', 'Gene') :: ['claudin-9'] @entity2 :: ('MESH:D008175', 'Disease') :: ['Lewis lung carcinoma', 'lung cancer'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis', 'Metastasis']
@entity3 :: (MESH:D009362,Disease) :: ['metastasis']
