Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis.

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.
Competing Interests: Declaration of interests J.D. has acted as a consultant for AstraZeneca, Bayer, Jubilant, Theras, BridgeBio, Vividion, and Novartis and has funded research agreements with Bristol Myers Squibb, Revolution Medicines, and Boehringer Ingelheim. E.W.T. is a founder and shareholder in Myricx Pharma, Ltd., and receives consultancy or research funding from Kura Oncology, Pfizer, Ltd., Samsara Therapeutics, Myricx Pharma, Ltd., MSD, Exscientia, and Daiichi Sankyo.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)