TY - UNPB
T1 - Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis
AU - Tomic, Goran
AU - Refermat, Alice Y.
AU - Sheridan, Clare
AU - Baggelaar, Marc
AU - Sipthorp, James
AU - Sudarshan, Bhuvana
AU - Ocasio, Cory A.
AU - Suárez-Bonnet, Alejandro
AU - Priestnall , Simon L.
AU - Herbert, Eleanor
AU - Tate, Edward W.
AU - Downward, Julian
PY - 2023/2/8
Y1 - 2023/2/8
N2 - 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.
AB - 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.
KW - Palmitoylation, Cancer, lipidation, ZDHHC20
U2 - 10.1101/2023.02.08.527637v2
DO - 10.1101/2023.02.08.527637v2
M3 - Preprint
T3 - bioRxiv
BT - Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis
PB - bioRxiv
ER -
