Abstract 5284: The Oncogenic Role of MALL in NSCLC

Abstract

Abstract MALL (T-cell differentiation protein-like) located on the human chromosome 2q13 locus encodes a 17.5KDa protein enriched in glycolipid and cholesterol enriched membrane raft (GEM). It is involved in the raft-mediated trafficking machinery in endothelial cells. Previous study showed that MALL can interact with Caveolin-1. However, Caveolin-1 can be phosphorylated by FAK and then promotes cell proliferation and colony formation in NSCLC (non-small cell lung cancer) cell lines. However, the role of MALL in cancer progression is totally unknown. In this study, we found that the expression of MALL is upregulated up to 250-fold in the high invasive lung cancer cells (CL1-5) than low invasive cells (CL1-0). To investigate the biological function of MALL, we first generated a constitutively MALL-expressed lung cancer cell line. We found that MALL can significantly enhance cancer invasiveness by the Boyden chamber matrigel assay (2.12 fold, p<0.01). MALL also promote cell migration by the transwell assay (1.53 fold, p<0.01) and wound healing assay. Moreover, MALL increased the colonogenesis of lung cancer cells by using an anchorage-dependent colony formation assay (1.73 fold, p=0.035) but did not affect the rate of cell proliferation by MTT assay. These findings indicated that MALL can promote tumor metastasis and tumorigenesis. To determine the underlying mechanisms by which MALL increases tumorigenesis and invasion Affymetrix oligonucleotide analysis was performed. The genes differentially expressed between MALL and mock transfectants with greater than two-fold change was identified by ANOVA analysis (FDR< 0.05). The most relevant networks involved were analyzed using MetaCore and IPA (ingenuity pathway analysis) software including cytoskeleton, ECM signaling, and other networks. Taken together, MALL may be a potential oncogene which might provide new insights into the future treatment of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5284.