title: Identification of ZDHHC14 as a novel human tumour suppressor gene.
abstract: 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 increased [CORRECTED] 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.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Yeste-Velasco
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
authors.forename: Richard
authors.initials: R
authors.lastname: Grose
authors.forename: Sakunthala C
authors.initials: SC
authors.lastname: Kudahetti
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lin
authors.forename: Jacek
authors.initials: J
authors.lastname: Marzec
authors.forename: Natasa
authors.initials: N
authors.lastname: Vasiljević
authors.forename: Tracy
authors.initials: T
authors.lastname: Chaplin
authors.forename: Liyan
authors.initials: L
authors.lastname: Xue
authors.forename: Maojia
authors.initials: M
authors.lastname: Xu
authors.forename: Julie M
authors.initials: JM
authors.lastname: Foster
authors.forename: Santi S
authors.initials: SS
authors.lastname: Karnam
authors.forename: Sharon Y
authors.initials: SY
authors.lastname: James
authors.forename: Athina-Myrto
authors.initials: AM
authors.lastname: Chioni
authors.forename: David
authors.initials: D
authors.lastname: Gould
authors.forename: Attila T
authors.initials: AT
authors.lastname: Lorincz
authors.forename: R Tim D
authors.initials: RT
authors.lastname: Oliver
authors.forename: Claude
authors.initials: C
authors.lastname: Chelala
authors.forename: Gareth M
authors.initials: GM
authors.lastname: Thomas
authors.forename: Janet M
authors.initials: JM
authors.lastname: Shipley
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mather
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009373:Neoplasms, Germ Cell and Embryonal / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D034622:RNA Interference; D013736:Testicular Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D000217:Acyltransferases; C557245:ZDHHC14 protein, human
keywords: ZDHHC14; apoptosis; prostate cancer; testicular germ cell tumours; tumour suppressor gene