Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis

Goran Tomic, Alice Y. Refermat, Clare Sheridan, Marc Baggelaar, James Sipthorp, Bhuvana Sudarshan, Cory A. Ocasio, Alejandro Suárez-Bonnet, Simon L. Priestnall , Eleanor Herbert, Edward W. Tate, Julian Downward*

*Corresponding author for this work

Research output: Working paperPreprintAcademic


Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo shRNA screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro, or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals, and in animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumour cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of novel substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.
Original languageEnglish
Number of pages22
Publication statusPublished - 8 Feb 2023
Externally publishedYes

Publication series

PublisherCold Spring Harbor Laboratory
ISSN (Print)2692-8205


  • Palmitoylation, Cancer, lipidation, ZDHHC20


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