Abstract 2106: The role of KSRP in non-small cell lung cancer

Abstract

Abstract Precedent has established the role of the Wnt/β-catenin pathway in oncogenesis. Several members of the Wnt family are known to be tumor promoting in non-small cell lung cancer, NSCLC. In this pathway β-catenin, a downstream component, accumulates and serves as a T-cell transcription /lymphoid enhancer factor. We previously identified the Wnt ligand in the lung, Wnt 7a, as a member of the non-canonical pathway/ β-catenin independent pathway, which inhibits transformed cell growth. Currently, we hypothesize that the regulatory protein, KSRP, holds a switch between the canonical and non-canonical pathway. K-homology splicing regulatory protein (KSRP) is a member of the family of AU rich element binding proteins. It possesses four K-homology motifs and causes decay of specific mRNA transcripts in different cell types. In mouse F9 teratocarcinoma cells KSRP negatively regulates β-catenin. The role of KSRP in the non-canonical Wnt pathway in the lung has previously been unknown. Using NSCLC cell lines and nontransformed lung cells we show a correlation between Wnt 7a expression and a positive regulation of KSRP. KSRP expression is elevated in nontransformed cells and alternatively, lower levels of KSRP expression in NSCLC. Over expression of KSRP in NSCLC cells decreases cell proliferation in MTS assay as well as reducing colony formation in clonogenic assays. The silencing of KSRP in nontransformed cells results in an increase in cell proliferation. The positive regulation of KSRP by Wnt 7a positively regulates this mRNA regulatory protein in the noncanonical Wnt pathway as an important factor in tumor suppression. The canonical pathway negatively regulates KSRP, which allows the stabilization of β-catenin mRNA thereby promoting progression of the tumor-promoting pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2106. doi:10.1158/1538-7445.AM2011-2106