Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo
IA Elsum, LL Yates, HB Pearson, TJ Phesse, F Long, R O'Donoghue, M Ernst, C Cullinane, PO Humbert
Oncogene | NATURE PUBLISHING GROUP | Published : 2014
Lung cancer is the leading cause of cancer deaths worldwide with non small-cell lung cancer (NSCLC) accounting for 80% of all lung cancers. Although activating mutations in genes of the RAS-MAPK pathway occur in up to 30% of all NSCLC, the cooperating genetic lesions that are required for lung cancer initiation and progression remain poorly understood. Here we identify a role for the cell polarity regulator Scribble (Scrib) in NSCLC. A survey of genomic databases reveals deregulation of SCRIB in human lung cancer and we show that Scrib(+/-) mutant mice develop lung cancer by 540 days with a penetrance of 43%. To model NSCLC development in vivo, we used the extensively characterized LSL-KRas(..View full abstract
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Awarded by NHMRC of Australia
We thank Dr Jason Li, Dr David Bimms, Sam Williams, Olivia Cakebread, Tanja Kinwel and the microscopy and histology core at the Peter MacCallum Cancer Centre. We also thank Dr Alison Dooley and Prof Roderick Bronson from the Massachusetts Institute of Technology for their technical advice and to Drs Helena Richardson and Sarah Russell for critical reading of the manuscript. This study was supported by grants from the NHMRC of Australia (no. 1025239 for TJP and RJO; no. 1004434 for IAE and LLY), Movember/PCFA and Richard Pratt Foundation (for HBP). IAE was supported by a Cancer Council Victoria Postgraduate Research Scholarship and POH was supported by a Biomedical Career Development Award from the NHMRC of Australia.