The Francis Crick Institute
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Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis.

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journal contribution
posted on 2024-05-13, 11:29 authored by Goran Tomić, Clare Sheridan, Alice Y Refermat, Marc P Baggelaar, James Sipthorp, Bhuvana Sudarshan, Cory A Ocasio, Alejandro Suárez-Bonnet, Simon L Priestnall, Eleanor Herbert, Edward W Tate, Julian Downward
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 short hairpin RNA (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 animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumor cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of 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.


Crick (Grant ID: CC2097, Grant title: Downward CC2097) Crick (Grant ID: CC1061, Grant title: STP Experimental Histopathology) Wellcome Trust (Grant ID: 103799/A/14/Z, Grant title: WT 103799/A/14/Z) European Research Council (Grant ID: 834692 - RASImmune, Grant title: ERC 834692 - RASImmune)