Abstract
Abstract We have discovered a potential oncogenic role of a gene in non-small cell lung cancer (NSCLC) using RNAi technology. Silencing of the gene significantly inhibits soft agar colony formation of NSCLC cell lines, whereas its inhibition on cell proliferation in liquid culture is modest. This effect was observed in multiple murine and human NSCLC cell lines with varied Kras and p53 status. The inhibition on soft agar colony formation is reversed with ectopic overexpression of a cDNA encoding the full-length gene. Knocking down the expression of the gene also significantly impairs migration and enhances detachment-induced anoikis of NSCLC cells. An investigation of the molecular mechanisms reveals that silencing of the gene cytoskeleton signaling network. In xenograft studies using stable luciferase-expressing inducible shRNA cell lines, silencing of the gene upon doxycycline treatment leads to a modest reduction in tumor volumes while significantly decreases bioluminescent signals at metastatic sites including lung and lymph nodes. Furthermore, gene expression analyses in KrasG12D/p53 deletion-driven mouse tumors and clinical tumor samples show significantly increased expression of the gene in lung cancer as well as multiple other cancer types. Taken together, we have uncovered a novel oncogenic function of a gene in NSCLC, which could provide a potential new therapeutic target for cancer intervention. Citation Format: Honglin Chen, James Lee, Noelyn M. Kljavin, Leisa Johnson, Yuxin Liang. Identification of a novel gene target involved in tumor growth and metastasis of non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3015. doi:10.1158/1538-7445.AM2013-3015 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Published Version
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