Open AccessProtocadherin‐8 promotes invasion and metastasis via laminin subunit γ2 in gastric cancer
Author(s) -
Lin Ying,
Ge Xiaoxiao,
Zhang Xiaofei,
Wu Zheng,
Liu Kaiyi,
Lin Fengjuan,
Dai Congqi,
Guo Weijian,
Li Jin
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13502
Subject(s) - metastasis , downregulation and upregulation , protocadherin , cancer research , cancer , biology , gene knockdown , ectopic expression , pathogenesis , laminin , pathology , cadherin , extracellular matrix , medicine , microbiology and biotechnology , immunology , gene , cell , genetics
Growing evidence suggests that protocadherins ( PCDH ) play crucial roles in pathogenesis and progression of cancers, including gastric cancer ( GC ). Protocadherin‐8 ( PCDH 8 ) was previously reported to be involved in metastasis of GC , but functional studies yielded inconsistent results and the molecular mechanism remained unknown. The present study aimed to explore the clinical relevance, function and molecular mechanism of PCDH 8 in GC . Data from the GEPIA and Kaplan–Meier plotter databases showed that high expression of PCDH 8 was significantly correlated with poorer prognosis in GC . Ectopic expression of PCDH 8 in GC cells promoted invasion and migration in vitro and metastasis in vivo, and knockdown of PCDH 8 inhibited invasion and migration in vitro. RNA sequencing followed by gene set enrichment analysis found a remarkable enrichment in the extracellular matrix receptor interaction pathway, with the expression of laminin subunit γ2 ( LAMC 2 ) being significantly increased in the PCDH 8‐overexpressing group. High expression of LAMC 2 was significantly correlated to poor prognosis in GC in GEPIA database. Upregulation of LAMC 2 following PCDH 8 overexpression was further confirmed by immunohistochemistry in liver metastatic lesions of nude mice. To our knowledge, this is the first report of the metastasis‐enhancing property and molecular mechanism through upregulation of LAMC 2 of PCDH 8 in cancer. High expression of PCDH 8 could be used as a biomarker for poor prognosis in clinical practice.