title: Loss of protocadherin-17 (PCDH-17) promotes metastasis and invasion through hyperactivation of EGFR/MEK/ERK signaling pathway in hepatocellular carcinoma.
abstract: Metastasis has been one of the major reasons for cancer-related mortality, with multiple genes and pathways being involved in this complex process. Given the molecular variations underlying metastasis of hepatocellular carcinoma (HCC) remains largely unknown; in our previous work, we found copying number of protocadherin-17 (PCDH-17) was significantly deleted in HCC tissues that occurred to metastasize compared with that in the primary HCC without metastasis. Therefore, we hypothesized that PCDH-17 may suppress the metastasis of HCC. There has been, however, no relevant literature available regarding PCDH-17 in HCC. In the present study, we have immunohistochemically detected and clinicopathologically analyzed the expression of PCDH-17 in vivo in clinical tissues; besides, we have explored the role of PCDH-17 ex vivo using a panel of HCC cell lines. It was discovered that PCDH-17 expression was clinically correlated with overall prognosis as well as metastasis in vivo and that PCDH-17 inhibited metastasis via EGFR/MEK/ERK signaling pathway ex vivo. Together, our results obtained both in vivo and ex vivo suggested that activation of EGFR/MEK/ERK signaling pathway through PCDH-17 promotes metastasis in HCC.
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dang
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Shangguan
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Yanshun
authors.initials: Y
authors.lastname: Ren
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lv
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China. Doctor_hjxiang@163.com.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xiang
authors.affiliation: The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People's Liberation Army, Lanzhou, Gansu, 730050, People's Republic of China. Doctor_xhwang@163.com.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015820:Cadherins; C529349:PCDH17 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: ERK; Hepatocellular carcinoma; Metastasis; Prognosis; Protocadherin-17 (PCDH-17)