Dev Proj 2: Optical Dissection of a Lung Cancer Tumor Suppressor Gene

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