Abstract 2059: NADPH Oxidase 4 induced ROS regulates anoikis resistance through activation of Src and EGFR
Abstract Since cancer cells must overcome the anoikis for the metastasis, anoikis resistance is an important process for tumor progression and metastasis. To identify anoikis resistance mechanism, we performed mRNA microarray analysis with attached and suspended human lung epithelial adenocarcinoma...
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| Published in: | Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.2059-2059 |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
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| Summary: | Abstract
Since cancer cells must overcome the anoikis for the metastasis, anoikis resistance is an important process for tumor progression and metastasis. To identify anoikis resistance mechanism, we performed mRNA microarray analysis with attached and suspended human lung epithelial adenocarcinoma A549 cells. Our microarray data reveals that Nox4 mRNA is up-regulated in the suspended cells. We evaluated both mRNA and protein levels of Nox4 and found that Nox4 is up-regulated in both mRNA and protein levels. In addition, higher levels of ROS are detected and Src activation was enhanced in suspended cells than attached cells. Interestingly, increased level of ROS in suspended cells was decreased by ROS scavengers or Nox4 inhibitors, leading to inactivation of Src and EGFR. Furthermore, knock-down of Nox4 by si-RNA specific for Nox4 resulted in inactivation of Src and EGFR. Because Src activation is not inhibited by EGFR inhibitor, Src activation appears to be independent on EGFR. In addition, si-RNA for Nox4 transfection decreased viability of cells in suspension. These results suggest that upon cell detachment, Nox4 expression is up-regulated and thus ROS levels are increased, which are important for activation of Src and EGFR, leading to sustained cell viability in the suspended cells. Therefore, we postulate that ROS generation through the Nox4 is an important process for anoikis resistance.
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 2059. doi:1538-7445.AM2012-2059 |
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| ISSN: | 0008-5472 1538-7445 |