We thank F. McCormick and M. Wang (UCSF) for sharing reagents and results, R. Shaw (Salk) for KPf/fL mice, M. Karin (UCSD) for mouse cancer samples and comments on the manuscript, H. Han and E. Menashi (Tgen) for experimental suggestions and reagents, J. Zimmerman and S. Simon for laboratory support, N. Cernac and J. Chang for laboratory assistance, J. Chambers and K. Suter-Brady for animal work, T. Zhang and K. Mcintyre for histology services. This work was supported by the following grants: Ministry of Science and Technology of China (2016YFA0501403) and National Natural Science Foundation of China (21575057) to R.T.; NIH CA014195, CA082683, CA080100, Lustgarten Foundation (awards 388246 and 552873), Helmsley Charitable Trust (2012-PG-MED002), and William Isacoff Research Foundation to T.H.; SU2C Pancreatic Cancer Dream Team (SU2C-AACR-DT-05-09, SU2C-AACR-DT-20-16) to D.D.V.H., R.M.E., G.W., T.H., A.M.L., T.R. and M.D.; NRSA F31CA206416 and T32GM007752 to N.K.L.; F32CA217033 to G.L.; Flinn Foundation to E.B.; NIH CA178015, CA227807 and CA222862 to E.A.C.; NIH CA197699 and CA186043 to T.R.; NIH CA155620 to A.M.L.; NIH P50CA127297, U01CA210240, P30CA36727 and 5R50CA211462 to P.M.G. and M.A.H. R.M.E. is a Howard Hughes Medical Institute Investigator and March of Dimes Chair in Molecular and Developmental Biology, and supported by Lustgarten, Ipsen/Biomeasure, Freeberg and William Isacoff Research Foundation. We thank Salk core facilities and staff, financially supported by NCI CCSG CA014195, including Advanced Biophotonics, Flow Cytometry, Functional Genomics, Integrative Genomics and Bioinformatics, Next Generation Sequencing and Transgenic Cores. Y.S. received a fellowship from the Helmsley Charitable Trust. T.H. is a Frank and Else Schilling American Cancer Society Professor and the Renato Dulbecco Chair in Cancer Research.

Reviewer information

Nature thanks Claus Jørgensen, Amina Ann Qutub and the other anonymous reviewer(s) for their contribution to the peer review of this work.