WISP-1 is a Wnt-1-and β-catenin-responsive oncogene

L Xu, RB Corcoran, JW Welsh, D Pennica… - Genes & …, 2000 - genesdev.cshlp.org
L Xu, RB Corcoran, JW Welsh, D Pennica, AJ Levine
Genes & development, 2000genesdev.cshlp.org
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 β-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 β-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 …
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 β-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 β-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.
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