Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer

被引:88
|
作者
Kwon, Chae Hwa [1 ,2 ,3 ]
Park, Hye Ji [1 ,2 ,3 ]
Choi, Jin Hwa [1 ,2 ,3 ]
Lee, Ja Rang [1 ,2 ,3 ]
Kim, Hye Kyung [1 ,2 ,3 ]
Jo, Hong-Jae [2 ,3 ,4 ]
Kim, Hyun Sung [2 ,3 ,4 ]
Oh, Nahmgun [2 ,3 ,4 ]
Song, Geun Am [2 ,3 ,5 ]
Park, Do Youn [1 ,2 ,3 ]
机构
[1] Pusan Natl Univ Hosp, Dept Pathol, Busan, South Korea
[2] Pusan Natl Univ, Sch Med, Busan, South Korea
[3] Pusan Natl Univ Hosp, Biomed Res Inst, Busan, South Korea
[4] Pusan Natl Univ Hosp, Dept Surg, Busan, South Korea
[5] Pusan Natl Univ Hosp, Dept Internal Med, Busan, South Korea
关键词
colorectal cancer; snail; serpinA1; prognosis; fibronectin; EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTIONAL REPRESSOR SNAIL; GENE-EXPRESSION; E-CADHERIN; CELL-LINES; ALPHA-1-ANTITRYPSIN; LUNG; INVASION; PROTEIN; PROSTATE;
D O I
10.18632/oncotarget.3964
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) in tumorigenesis has been previously identified. However, the exact role and mechanism of these proteins in progression of colorectal cancer (CRC) are controversial. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling was involved in CRC cell invasion and migration. Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC.
引用
收藏
页码:20312 / 20326
页数:15
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