The complex roles of Wnt antagonists in RCC

Sharanjot Saini, Shahana Majid, Rajvir Dahiya

Research output: Contribution to journalReview article

23 Scopus citations

Abstract

Renal cell carcinoma (RCC) is the most lethal of all the genitourinary cancers, as it is generally refractory to current treatment regimens, including chemotherapy and radiation therapy. Targeted therapies against critical signaling pathways associated with RCC pathogenesis, such as vascular endothelial growth factor, von Hippel - Lindau tumor suppressor and mammalian target of rapamycin, have shown limited efficacy so far. Thus, Wnt signaling, which is known to be intricately involved in the pathogenesis of RCC, has attracted much interest. Several Wnt signaling components have been examined in RCC, and, while studies suggest that Wnt signaling is constitutively active in RCC, the molecular mechanisms differ considerably from other human carcinomas. Increasing evidence indicates that secreted Wnt antagonists have important roles in RCC pathogenesis. Considering these vital roles, it has been postulated - and supported by experimental evidence - that the functional loss of Wnt antagonists, for example by promoter hypermethylation, can contribute to constitutive activation of the Wnt pathway, resulting in carcinogenesis through dysregulation of cell proliferation and differentiation. However, subsequent functional studies of these Wnt antagonists have demonstrated the inherent complexities underlying their role in RCC pathogenesis.

Original languageEnglish (US)
Pages (from-to)690-699
Number of pages10
JournalNature Reviews Urology
Volume8
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Urology

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