The EMT-activator Zeb1 is crucial for cellular plasticity and drives metastasis in pancreatic cancer. Mus musculus

Depletion of Zeb1 in a KPC-model for pancreatic cancer affected strongly the formation of precursor lesions, tumour grading, invasion and notably metastasis during PDAC progression. In this context, EMT is important for metastasis, but there is variability and specificity (and not redundancy) in the role and function of different EMT-inducing transcription factors. Overall design: Primary Tumor cell lines were derived in replicates from pancreatic cancer driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC-model) and also from Pdx1-Cre;Zeb1fl/fl with KrasLSL.G12D/+;Tp53LSL.R172H/+;Zeb1fl/fl mice (KPCZ, Zeb1 knockout). The tumor cell lines displayed phenotypes from mesenchymal and epithelial (designated as KPC_E, KPCZ_E or KPC_M). Two epithelial KPC cell lines and two KPCZ cell lines were treated with 5ng/ml TGFβ (KPC_E+TGFβ or KPCZ_E+TGFβ)