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

Oncogene volume 20, pages 5525–5532 (2001)Cite this article

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 WISP1v, 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.

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References

  • Babic AM, Kireeva ML, Kolesnikova TV, Lau LF . 1998 Proc. Natl. Acad. Sci. USA 95: 6355–6360

  • Babic AM, Chen CC, Lau LF . 1999 Mol. Cell. Biol. 19: 2958–2966

  • Bork P . 1993 FEBS Lett. 327: 125–130

  • Brigstock DR . 1999 Endocr. Rev. 20: 189–206

  • Chen N, Chen CC, Lau LF . 2000 J. Biol. Chem. 275: 24953–24961

  • Chung LW . 1995 Cancer Surv. 23: 33–42

  • Hadjiargyrou M, Ahrens W, Rubin CT . 2000 J. Bone Miner. Res. 15: 1014–1023

  • Hashimoto Y, Shindo-Okada N, Tani M, Nagamachi Y, Takeuchi K, Shiroishi T, Toma H, Yokota J . 1998 J. Exp. Med. 187: 289–296

  • Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A . 2001 J. Biol. Chem. 276: 10594–10601

  • Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J, Holderbaum D, Pauli RM, Herd JK, Van Hul EV, Rezai-Delui H, Legius E, Le Merrer M, Al-Alami J, Bahabri SA, Warman ML . 1999 Nat. Genet. 23: 94–98

  • Joliot V, Martinerie C, Dambrine G, Plassiart G, Brisac M, Crochet J, Perbal B . 1992 Mol. Cell. Biol. 12: 10–21

  • Kireeva ML, Mo F, Yang GP, Lau LF . 1996 Mol. Cell. Biol. 16: 1326–1334

  • Kitamura K, Beppu R, Anai H, Ikejiri K, Yakabe S, Sugimachi K, Saku M . 1995 J. Surg. Oncol. 58: 112–117

  • Kumar S, Hand AT, Connor JR, Dodds RA, Ryan PJ, Trill JJ, Fisher SM, Nuttall ME, Lipshutz DB, Zou C, Hwang SM, Votta BJ, James IE, Rieman DJ, Gowen M, Lee JC . 1999 J. Biol. Chem. 274: 17123–17131

  • Maehara Y, Kakeji Y, Kabashima A, Emi Y, Watanabe A, Akazawa K, Baba H, Kohnoe S, Sugimachi K . 1999 J. Clin. Oncol. 17: 607–614

  • Peifer M, Polakis P . 2000 Science 287: 1606–1609

  • Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhern MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ . 1998 Proc. Natl. Acad. Sci. USA 95: 14717–14722

  • Scholz G, Martinerie C, Perbal B, Hanafusa H . 1996 Mol. Cell. Biol. 16: 481–486

  • Shi-wen X, Pennington D, Holmes A, Leask A, Bradham D, Beauchamp JR, Fonseca C, du Bois RM, Martin GR, Black CM, Abraham DJ . 2000 Exp. Cell Res. 259: 213–224

  • Sugimachi K . 1993 Curr. Opin. Gen. Surg. 1: 216–218

  • Tanaka S, Ito T, Wands JR . 1996 J. Biol. Chem. 271: 14610–14616

  • Tanaka S, Akiyoshi T, Mori M, Wands JR, Sugimachi K . 1998 Proc. Natl. Acad. Sci. USA 95: 10164–10169

  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN . 1998 Cell 93: 705–716

  • Xu L, Corcoran RB, Welsh JW, Pennica D, Levine AJ . 2000 Genes. Dev. 14: 585–595

  • Zhang R, Averboukh L, Zhu W, Zhang H, Jo H, Dempsey PJ, Coffey RJ, Pardee AB, Liang P . 1998 Mol. Cell. Biol. 18: 6131–6141

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Acknowledgements

We thank Dr Dianne Pennica (Genetech Inc.) and Prof Jack R Wands (Brown University) for helpful discussions; and Ms M Hirata and M Kubota for technical assistance. This work was supported by NOVARTIS Foundation for the Promotion of Science, Sagawa Cancer Research Fund, Fukuoka Cancer Research Foundation, and Grant-in-Aid from the Ministry of Education, Science, Technology, Sports and Culture of Japan. S Tanaka is a recipient of the Japan Cancer Society Incitement Award.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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

  2. Station for Collaborative Research, Kyushu University, Fukuoka, Japan

    Keizo Sugimachi

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  1. Shinji Tanaka
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Correspondence to Shinji Tanaka.

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Tanaka, S., Sugimachi, K., Saeki, H. et al. A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. Oncogene 20, 5525–5532 (2001). https://doi.org/10.1038/sj.onc.1204723

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