LGR5 promotes hepatocellular carcinoma metastasis through inducting epithelial-mesenchymal transition

被引:22
作者
Liu, Jie [1 ,2 ]
Yu, Guo-Zheng [3 ]
Cheng, Xiao-Ke [4 ]
Li, Xiao-Dong [4 ,5 ]
Zeng, Xian-Tao [6 ]
Ren, Xue-Qun [1 ,4 ]
机构
[1] Henan Univ, Huaihe Hosp, Dept Gen Surg, Kaifeng 475000, Henan, Peoples R China
[2] Henan Univ, Huaihe Hosp, Nursing Dept, Kaifeng 475000, Henan, Peoples R China
[3] Hubei Polytech Univ, Affiliated Hosp, Huangshi Cent Hosp, Dept Gen Surg, Huangshi 435000, Hubei, Peoples R China
[4] Henan Univ, Huaihe Hosp, Ctr Evidence Based Med, Kaifeng 475000, Henan, Peoples R China
[5] Henan Univ, Huaihe Hosp, Dept Urol, Kaifeng 475000, Henan, Peoples R China
[6] Wuhan Univ, Zhongnan Hosp, Ctr Evidence Based & Translat Med, Wuhan 430071, Hubei, Peoples R China
关键词
hepatocellular carcinoma; LGR5; leucine-rich repeat-containing G-protein coupled receptor 5; metastasis; epithelial-mesenchymal transition; PROTEIN-COUPLED RECEPTOR; BETA-CATENIN; EPIDEMIOLOGY; OVEREXPRESSION; PROGRESSION; GPR49;
D O I
10.18632/oncotarget.15143
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The purpose of the present study was to investigate the prognostic value of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. The expression level of LGR5 in liver tumor tissues and adjacent non-tumor tissues were detected adopting immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. Chi-square test was used to evaluate the correlation between LGR5 expression and clinicopathological characteristics. In addition, we assessed the relationship between LGR5 and two epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) in HCC tissues and cell lines. Our results showed that the expression of LGR5 was significantly higher in liver tumor tissues than in adjacent non-tumor tissues. Moreover, up-regulated LGR5 was associated with larger tumor diameter (> 5cm, P=0.001), higher TNM stage (P=0.021), increased recurrence (P=0.023) and growing metastasis (P=0.030). Besides, we found that the expression level of LGR5 was correlated with E-cadherin and N-cadherin. In conclusion, up-regulated LGR5 in HCC patients is associated with malignant clinicopathological characteristics. LGR5 may promote HCC metastasis through inducting EMT process, and thus can be regarded as a candidate biomarker for prognosis and as a target in therapy.
引用
收藏
页码:50896 / 50903
页数:8
相关论文
共 18 条
[1]  
Dhanasekaran R, 2012, HEPATIC MED-EVID RES, V4, P19, DOI [10.1586/egh.09.35, 10.2147/HMER.S16316]
[2]   Epithelial-mesenchymal transition in the liver [J].
Firrincieli, D. ;
Boissan, M. ;
Chignard, N. .
GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE, 2010, 34 (10) :523-528
[3]   Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis [J].
Gomaa, Asmaa Ibrahim ;
Khan, Shahid A. ;
Toledano, Mireille B. ;
Waked, Imam ;
Taylor-Robinson, Simon D. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (27) :4300-4308
[4]   Epithelial-mesenchymal transition and tumour invasion [J].
Guarino, Marcello .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2007, 39 (12) :2153-2160
[5]   Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region [J].
Hsu, SY ;
Liang, SG ;
Hsueh, AJW .
MOLECULAR ENDOCRINOLOGY, 1998, 12 (12) :1830-1845
[6]   The role of microRNAs in liver cancer progression [J].
Huang, S. ;
He, X. .
BRITISH JOURNAL OF CANCER, 2011, 104 (02) :235-240
[7]   CD151 Amplifies Signaling by Integrin α6β1 to PI3K and Induces the Epithelial-Mesenchymal Transition in HCC Cells [J].
Ke, Ai-Wu ;
Shi, Guo-Ming ;
Zhou, Jian ;
Huang, Xiao-Yong ;
Shi, Ying-Hong ;
Ding, Zhen-Bin ;
Wang, Xiao-Ying ;
Devbhandari, Ranjan Prasad ;
Fan, Jia .
GASTROENTEROLOGY, 2011, 140 (05) :1629-U389
[8]   Epidemiology of chronic hepatitis B virus infection, hepatocellular carcinoma, and hepatitis B virus-induced hepatocellular carcinoma [J].
Kew, M. C. .
PATHOLOGIE BIOLOGIE, 2010, 58 (04) :273-277
[9]   Hepatocellular carcinoma: Epidemiology and clinical aspects [J].
Mazzanti, Roberto ;
Gramantieri, Laura ;
Bolondi, Luigi .
MOLECULAR ASPECTS OF MEDICINE, 2008, 29 (1-2) :130-143
[10]   Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors [J].
McClanahan, Terrill ;
Koseoglu, Sandra ;
Smith, Kathleen ;
Grein, Jeffrey ;
Gustafson, Eric ;
Black, Stuart ;
Kirschmeier, Paul ;
Samatar, Ahmed A. .
CANCER BIOLOGY & THERAPY, 2006, 5 (04) :419-426