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Identification of ZDHHC14 as a novel human tumour suppressor gene
Author(s) -
YesteVelasco Marc,
Mao Xueying,
Grose Richard,
Kudahetti Sakunthala C,
Lin Dongmei,
Marzec Jacek,
Vasiljević Natasa,
Chaplin Tracy,
Xue Liyan,
Xu Maojia,
Foster Julie M,
Karnam Santi S,
James Sharon Y,
Chioni AthinaMyrto,
Gould David,
Lorincz Attila T,
Oliver R Tim D,
Chelala Claude,
Thomas Gareth M,
Shipley Janet M,
Mather Stephen J,
Berney Daniel M,
Young Bryan D,
Lu YongJie
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4327
Subject(s) - biology , suppressor , cancer research , tumor suppressor gene , gene , germ cell , prostate cancer , cancer , cell growth , apoptosis , cell , microbiology and biotechnology , genetics , carcinogenesis
Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14 . The expression of ZDHHC14 , a putative protein palmitoyltransferase with unknown cellular function, was decreased at both RNA and protein levels in testicular germ cell tumours. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. In addition to our findings of genetic and protein expression changes in clinical samples, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspase‐dependent apoptotic pathway and heterozygous knockout of ZDHHC14 decreased cell colony formation ability. Finally, we confirmed our in vitro findings of the tumour suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumourigenesis. Thus, we have identified a novel tumour suppressor gene that is commonly down‐regulated in testicular germ cell tumours and prostate cancer, as well as given insight into the cellular functional role of ZDHHC14 , a potential protein palmitoyltransferase that may play a key protective role in cancer. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.