Abstract 352: hnRNP A2/B1 regulates S1PR3 expression in lung cancer
Authors: Jordi Tauler, Jessica Siegler, Xiaoguang Sun, Liliana Moreno-Vinasco, Joe GN Garcia
Journal: Cancer Research (2012)

Abstract Several clinical trials have shown that elevated expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) in exfoliated bronchial epithelial cells correlates with eventual development of lung cancer. Cells with high levels of hnRNP A2/B1 expression have also been reported to manifest multiple molecular features of genetic injury. The hnRNPs are a complex group of RNA-binding proteins which play a key role in mRNA processing: stability, splicing, export and subcellular localization and participate also in telomere biogenesis. To elucidate the mechanism that links hnRNP A2/B1 overexpression with lung cancer progression we have knocked down hnRNPA2/B1 mRNA in non-small cell lung cancer (NSCLC) cell line A549 with a stable siRNA vector-based system. Silencing hnRNP A2/B1 increased proliferation and decreased migration in A549 and H1703 cell lines. These changes in migration and proliferation in A549 and H1703 hnRNPA2/B1-silenced cell lines correlated with an increase of E-Cadherin expression in both cell lines at mRNA and protein level. This increase in E-Cadherin expression was accompanied with a down-regulation of E-Cadherin inhibitors Twist1 and Snai1. We have proposed that hnRNP A2/B1 modulates epithelial-mesenchymal transition (EMT) in lung cancer cell lines that present a mesenchymal or intermediate phenotype such as H1703 and A549. It has been proposed that EMT may induce metastasis of cells with a mesenchymal phenotype. After metastatic seeding, EMT would be reversed trough mesenchymal-epithelial transition (MET) allowing tumor growth. However, mechanisms that regulate reversion of EMT are still poorly characterized. Interestingly, sphingosine 1-phospate (S1P) is an important angiogenic factor and regulator of vascular permeability. Microarray expression analysis revealed that silencing hnRNP A2/B1 decreases expression of the sphingosine 1-phosphate receptor 3 (S1PR3), a pro-migration RhoGTPAse activating S1P receptor, in A549 cells. Therefore, Moreover, S1P also stimulates motility of cancer cells through S1P receptors. It has been described that S1PR3 regulates migration and invasion in breast, prostate and gastric cancer. In A549 cells, S1PR3 is the most abundant receptor for S1P. Here we report that down regulation of hnRNP A2/B1, in lung cancer cells, decreases S1PR3 expression at the mRNA and protein level. We propose that further study of the mechanistic link between hnRNP A2/B1, S1P function and S1P receptors may allow a better understanding of the molecular mechanisms involved in invasion, metastasis. It may also provide new insights regarding the interaction between endothelial and epithelial cells and the regulation of EMT during tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 352. doi:1538-7445.AM2012-352