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Investigating the role of the Wnt pathway in non-small cell lung cancer Lee, Eric Hung Leung

Abstract

Wnt signaling pathway has recently been recognized as a critical pathway in lung carcinogenesis. Some of the cancers that the Wnt pathway is involved in include colorectal, and breast cancers. However, the roles of Wnt pathway components are contradictory as well. These ambiguities are a result of multiple branch paths that it is associated with. In particular, the Wnt pathway is branched off into the canonical and non-canonical subpaths, of which, each subpath crosstalks with other pathways. Many studies have been done in an effort to decipher the behaviour of Wnt components in lung cancer through gene silencing techniques and knock-out models of a particular gene however a coordinated expression of Wnt components in the context of defining the involvement of the canonical and non-canonical pathways have not been explored. We investigated the role of the Wnt pathway in lung squamous cell carcinoma (SCC) by first establishing normal expression patterns of Wnt components in normal lung and deducing the aberrant expression of key components of the canonical and non-canonical pathway in tumor. In this study, 19 Wnt pathway genes representative of both canonical and non-canonical pathway were chosen for expression analysis via relative RT-PCR. The data suggested that both the canonical and non-canonical pathways are active in the normal lungs. In lung tumor, the expression of β-catenin/canconical pathway is surprisingly down-regulated in 50% of the samples while the non-canonical pathway components are up-regulated. These findings provide evidence that not all lung tumors are affected by the canonical Wnt pathway and that the non-canonical pathway may serve to be just as important in driving the proliferation of lung cancer cells.

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