WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene.
WISP-1 (Wnt-1 induced secreted protein 1) is a member of the CCN family of growth factors. This study identifies WISP-1 as a beta-catenin-regulated gene that can contribute to tumorigenesis. The promoter of WISP-1 was cloned and shown to be activated by both Wnt-1 and beta-catenin expression. TCF/LEF sites played a minor role, whereas the CREB site played an important role in this transcriptional activation. WISP-1 demonstrated oncogenic activities; overexpression of WISP-1 in normal rat kidney fibroblast cells (NRK-49F) induced morphological transformation, accelerated cell growth, and enhanced saturation density. Although these cells did not acquire anchorage-independent growth in soft agar, they readily formed tumors in nude mice, suggesting that appropriate cellular attachment is important for signaling oncogenic events downstream of WISP-1.
Xu
L
L
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Corcoran
R B
RB
Welsh
J W
JW
Pennica
D
D
Levine
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055511:CCN Intercellular Signaling Proteins; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D007668:Kidney; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; C492066:CCN4 protein, rat; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D006133:Growth Substances; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D051176:beta Catenin