BPB Reports

Paper Details

BPB Reports
Vol. 4 No. 4 p.103-111 2021
Regular Article
Elevated Expression of CELSR1 is Associated with Peritoneal Metastasis in Human Scirrhous Gastric Cancers
  • Yoshifumi Takei (Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University / takei@dpc.agu.ac.jp)
Toshifumi Hara 1) , Yuri Nomura 1) , Masaaki Hattori 1) , Keichiro Mihara 2) 3) , Kazuyoshi Yanagihara 4) , Yoshifumi Takei 1)
1) Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University , 2) Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , 3) Department of International Center for Cell and Gene Therapy, Fujita Health University , 4) Division of Translational Research, Exploratory Oncology and Clinical Trial Center, National Cancer Center
Received: July 17, 2021;   Accepted: July 19, 2021;   Released: August 13, 2021
Keywords: scirrhous gastric cancer, peritoneal metastasis, invasion, short hairpin RNA, focal adhesion kinase

Cancer metastasis is the leading cause of death in patients with any type of solid cancer. To develop effective cancer treatments, it is essential to understand the molecular mechanisms underlying cancer metastasis. Previously we established peritoneal metastasis cell models derived from human scirrhous gastric cancer patients. In this article, we focus on the CELSR1 gene, which is involved in Wnt signaling but whose association with peritoneal metastasis is still unclear. We unveiled gene alterations and the prognostic relevance of the CELSR1 gene in cancer patients by analyzing public resources for cancer genomic and patient cohorts. RT-qPCR and immunoblot analyses revealed that CELSR1 expression was significantly elevated in our cell lines, which had high peritoneal metastatic property, compared with their parental cell lines, which had lower peritoneal metastatic property. Some of the gene alterations in the coding region of CELSR1 were observed in our metastatic cell lines, but they were not associated with the metastatic property or with patient prognosis. Knockdown of CELSR1 via the shRNA technique significantly decreased migration and invasion in the cell lines having high peritoneal metastatic property, whereas the knockdown did not significantly affect proliferation. These results show that CELSR1 plays an important role in peritoneal metastasis and that CELSR1 is a novel peritoneal metastasisassociated gene. The results also suggest that CELSR1 is a proper molecular target for therapy against peritoneal metastasis of scirrhous gastric cancers.