Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway

脂质运载蛋白 上皮-间质转换 肝细胞癌 癌症研究 生物 转化生长因子 过渡(遗传学) 表皮生长因子 转化生长因子β 内科学 病理 医学 基因 遗传学 受体
作者
Yunpeng Wang,Goung‐Ran Yu,Mi-Jin Lee,Sang-Yeop Lee,In‐Sun Chu,Sun‐Hee Leem,Dae‐Ghon Kim
出处
期刊:Hepatology [Lippincott Williams & Wilkins]
卷期号:58 (4): 1349-1361 被引量:80
标识
DOI:10.1002/hep.26467
摘要

Lipocalin-2 (Lcn2) is preferentially expressed in hepatocellular carcinoma (HCC). However, the functional role of Lcn2 in HCC progression is still poorly understood, particularly with respect to its involvement in invasion and metastasis. The purpose of this study was to investigate whether Lcn2 is associated with the epithelial-mesenchymal transition (EMT) in HCC and to elucidate the underlying signaling pathway(s). Lcn2 was preferentially expressed in well-differentiated HCC versus liver cirrhosis tissues, and its expression was positively correlated with the stage of HCC. The characteristics of EMT were reversed by adenoviral transduction of Lcn2 into SH-J1 cells, including the down-regulation of N-cadherin, vimentin, alpha-smooth muscle actin, and fibronectin, and the concomitant up-regulation of CK8, CK18, and desmoplakin I/II. Knockdown of Lcn2 by short hairpin RNA (shRNA) in HKK-2 cells expressing high levels of Lcn2 was associated with EMT. Epidermal growth factor (EGF) or transforming growth factor beta1 (TGF-β1) treatment resulted in down-regulation of Lcn2, accompanied by an increase in Twist1 expression and EMT in HCC cells. Stable Lcn2 expression in SH-J1 cells reduced Twist1 expression, inhibited cell proliferation and invasion in vitro, and suppressed tumor growth and metastasis in a mouse model. Furthermore, EGF or TGF-β1 treatment barely changed EMT marker expression in SH-J1 cells ectopically expressing Lcn2. Ectopic expression of Twist1 induced EMT marker expression even in cells expressing Lcn2, indicating that Lcn2 functions downstream of growth factors and upstream of Twist1.Together, our findings indicate that Lcn2 can negatively modulate the EMT in HCC cells through an EGF (or TGF-β1)/Lcn2/Twist1 pathway. Thus, Lcn2 may be a candidate metastasis suppressor and a potential therapeutic target in HCC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
迷人的寒风完成签到,获得积分10
刚刚
刚刚
water应助科研通管家采纳,获得10
1秒前
Lucas应助HHHAN采纳,获得10
3秒前
无情修杰完成签到 ,获得积分10
4秒前
小柒完成签到 ,获得积分10
6秒前
聪慧芷巧发布了新的文献求助10
7秒前
8秒前
12秒前
蓝意完成签到,获得积分0
13秒前
xiaohongmao完成签到,获得积分10
18秒前
21秒前
qweerrtt完成签到,获得积分10
28秒前
28秒前
与共发布了新的文献求助10
29秒前
carly完成签到 ,获得积分10
30秒前
颢懿完成签到 ,获得积分10
33秒前
量子星尘发布了新的文献求助10
34秒前
36秒前
ljc完成签到 ,获得积分10
37秒前
Java完成签到,获得积分10
41秒前
43秒前
鲤鱼安青完成签到 ,获得积分10
45秒前
45秒前
dollarpuff完成签到 ,获得积分10
48秒前
48秒前
mmmmmMM完成签到,获得积分10
55秒前
luckweb完成签到,获得积分10
1分钟前
猫的毛完成签到 ,获得积分10
1分钟前
nicky完成签到 ,获得积分10
1分钟前
麦子完成签到 ,获得积分10
1分钟前
1分钟前
Wilson完成签到 ,获得积分10
1分钟前
luckweb发布了新的文献求助10
1分钟前
1分钟前
1分钟前
1分钟前
传奇3应助wujiwuhui采纳,获得10
1分钟前
开心寄松完成签到,获得积分10
1分钟前
北宫完成签到 ,获得积分10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022