L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer
Open Access
- 27 June 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 6 (1), 43-14
- https://doi.org/10.1186/1756-8722-6-43
Abstract
Background: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring. Methods: Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated. Results: L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA. Conclusions: Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.Keywords
This publication has 59 references indexed in Scilit:
- Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cellsJournal of Hematology & Oncology, 2013
- Prognostic relevance of melanoma antigen D1 expression in colorectal carcinomaJournal of Translational Medicine, 2012
- L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cellsCancer Letters, 2012
- High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphomaJournal of Hematology & Oncology, 2011
- L1 stimulation of human glioma cell motility correlates with FAK activationJournal of Neuro-Oncology, 2011
- Targeting Cancer Stem Cells through L1CAM Suppresses Glioma GrowthCancer Research, 2008
- The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodiesOncogene, 2007
- AKT/PKB Signaling: Navigating DownstreamCell, 2007
- Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cellsOncogene, 2006
- Extracellular Signal-regulated Kinase (ERK)-dependent Gene Expression Contributes to L1 Cell Adhesion Molecule-dependent Motility and InvasionOnline Journal of Public Health Informatics, 2004