Figure 2.

LOX expression is required for invasion in a mutant p53-driven model of PDAC

1. PC-1 signature is predictive of metastatic disease in mouse models of pancreatic cancer. Log-transformed expressions of signature transcripts from mouse tumor microarrays were mean-centered across samples and scaled to unit variance. These values were then multiplied by the matching loading values from the PC-1 signature and summarized for each sample across all transcripts to yield the risk score for that sample.
2. Inverted invasion assays were performed with PDAC tumor cell lines from KPC and KP^flC mice. Tumor cell lines bearing mutant p53^R172H (KPC) invade significantly further than tumor cells with deletion of 1 copy of p53 (KP^flC) (P ≤ 0.01). Data are shown as the average of four wells + SEM.
3. Introduction of shRNA targeting Lox into KPC tumor cells significantly inhibits invasion (P ≤ 0.01 by unpaired Student’s t-test). Data are shown as the average of four wells + SEM.
4. Introduction of exogenous LOX into KP^flC tumor cells significantly promotes invasion (left panel, P ≤ 0.01 by unpaired Student’s t-test). LOX expression was assessed by immunoblotting (right panel). Columns indicate the mean of four well and error bars indicate SEM.
5. Integration of heterogeneous data sets identifies LOX as a therapeutic target in pancreatic cancer. Components of the hazardous PC-1 signature are overlaid with genes found to be overexpressed in a microarray and hits that cause a reduction in viable cell number in an RNAi functional screen. Overlap is shown as a proportional Venn diagram.

Source data are available online for this figure.