A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma.
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.
Tanaka
S
S
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. shinjit@surg2.med.kyushu-u.ac.jp
Sugimachi
K
K
Saeki
H
H
Kinoshita
J
J
Ohga
T
T
Shimada
M
M
Maehara
Y
Y
Sugimachi
K
K
D016475:3T3 Cells; D002293:Adenocarcinoma, Scirrhous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014841:von Willebrand Factor / Q000737:chemistry
D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C492067:CCN4 protein, mouse; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D014841:von Willebrand Factor