The Role of Ring domain AP-1 Coactivator (RACO)-1 in Lung cancer

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Lung cancer is one of the most prevalent human cancers. Activating mutations of the K-Ras oncogene are found in 20-30% of non-small-cell lung cancers. Recently, a population of stem cells referred to as bronchioalveolar stem cells, has been identified at the bronchioalveolar duct junctions of the lung. It has been proposed that these stem cells are the precursors of K-Ras lung adenocarcinomas. MAP kinase pathways have been shown to be important in controlling the homeostasis of this cell population. The AP-1 transcription factor is believed to be an important mediator of oncogenic Ras signalling, however the molecular connection between oncogenic Ras and c-Jun/AP-1 has been unclear. The host lab has recently identified a previously uncharacterized protein, named Ring domain AP-1 Coactivator (RACO)-1 which functions as a molecular link between Ras-Raf-MEK-ERK MAP kinase pathways and AP-1 activation. In this proposal, I will investigate the role of RACO-1 in lung stem cell homeostasis and in K-Ras-induced lung tumours. The goal of this project is to understand the molecular mechanisms of co-operation between two well-defined oncogenes. Ras and c-Jun/AP-1, in the development of a highly relevant and prevalent form of cancer.