A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma

Shinji Tanaka, Keishi Sugimachi, Hiroshi Saeki, Junko Kinoshita, Takefumi Ohga, Mitsuo Shimada, Yoshihiko Maehara, Keizo Sugimachi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WlSP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.

Original languageEnglish
Pages (from-to)5525-5532
Number of pages8
JournalOncogene
Volume20
Issue number39
DOIs
Publication statusPublished - Sep 6 2001

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Tanaka, S., Sugimachi, K., Saeki, H., Kinoshita, J., Ohga, T., Shimada, M., Maehara, Y., & Sugimachi, K. (2001). A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. Oncogene, 20(39), 5525-5532. https://doi.org/10.1038/sj.onc.1204723