Pilot Project 2: Optical dissection of a lung cancer tumor suppressor gene PI: Adam I. Marcus, PhDTumor metastasis is the primary cause of patient death in almost all cancers. Attempts at developing atherapeutic strategy that can block metastasis is limited by our understanding of how stationary cancer cellstransform into malignant carcinomas. It is already known that one key step is the inactivation of tumorsuppressor genes, which allows cancer cells to continuously proliferate and eventually metastasize. In nonsmallcell lung cancer (NSCLC) the tumor suppressor gene, LKB1 is mutated in 30% of all primary tumors. Aseries of studies in normal epithelial cells implicate LKB1 as a master regulator of epithelial cell polarity raisingthe possibility that in NSCLC, LKB1 loss triggers an aberrant cell polarity program and subsequent cellinvasion. Interestingly, our preliminary data implicate LKB1 in NSCLC motility and migration; therefore, we willtest the hypothesis that LKB1 loss in NSCLC eliminates the activity of this suppressor and triggers cancer cellinvasion. These studies will rely on live cell confocal imaging to determine how LKB1 mediates NSCLCinvasion. Importantly, these mechanistic initiatives will be bridged with more translational studies investigatingthe impact of LKB1 loss on cancer cell invasion
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