Abstract 3218: Interrogating the role of NOX4 in colon cancer metastasis
| Autor: | Kerry M. Bauer, Amanda B. Hummon, Steven Buechler |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:3218-3218 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. Molecular biomarkers are used to partition tumors into a poor prognosis group that is likely to metastasize and a good prognosis group that has a higher probability to be relapse-free. These biomarkers for relapse risk are of clinical interest, and lead to insight into how a tumor progresses to metastasis. There is increasing evidence that cancer of the ascending (right-side) colon is different from the descending (left-side) colon. There are site-specific differences in histological and molecular characteristics and different signaling pathways have been shown to dominate progression to relapse in right and left-side colon cancer. We have observed that the genes altered in expression between the poor prognosis and good prognosis tumors vary significantly depending on whether the malignancy originates on the right or left side of the colon. We have identified NADPH oxidase 4 (NOX4) to be highly predictive of relapse in stage II and stage III left-side colon cancer where elevated expression of NOX4 is correlated with relapse. Furthermore, NOX4 expression is greatly elevated in the human colon cancer derived metastatic cell line SW620 compared to human cell lines derived from primary adenoma or carcinoma colon tumors. NOX4 silencing using RNA interference results in decreased levels of reactive oxygen species (ROS). The NOX family of genes has been implicated in cancer development in several types of cancer while overproduction of ROS has been implicated in tumor metastasis. We are exploring the newly identified role of NOX4-mediated ROS generation in metastatic colon cancer. To investigate the underlying molecular mechanism we are analyzing the effect of NOX4 silencing via RNA interference and NOX4 inhibition using pharmacological NOX inhibitors on global protein expression patterns in metastatic-derived SW620 cells. Proteomic changes are being assessed by iTRAQ labeling and mass spectrometry. Bioinformatics and cluster analysis will be used to identify the functional role of redox responsive and ROS regulative proteins in colon cancer metastasis. The role of NOX4 as a prognostic biomarker in colon cancer makes it an important target for research in cancer biology and therapeutics. Citation Format: Kerry M. Bauer, Steven Buechler, Amanda B. Hummon. Interrogating the role of NOX4 in colon cancer metastasis. [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 3218. doi:10.1158/1538-7445.AM2013-3218 |
| Databáze: | OpenAIRE |
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