Systematic siRNA screen unmasks NSCLC growth dependence by palmitoyltransferase DHHC5

Tian, Hui, Lu, Jui-Yun, Shao, Chunli, Huffman, Kenneth E., Carstens, Ryan M., Larsen, Jill E., Girard, Luc, Liu, Hui, Rodriguez-Canales, Jaime, Frenkel, Eugene P., Wistuba, Ignacio I., Minna, John D. and Hofmann, Sandra L. (2015) Systematic siRNA screen unmasks NSCLC growth dependence by palmitoyltransferase DHHC5. Molecular Cancer Research, 13 4: 784-794. doi:10.1158/1541-7786.MCR-14-0608

Author Tian, Hui
Lu, Jui-Yun
Shao, Chunli
Huffman, Kenneth E.
Carstens, Ryan M.
Larsen, Jill E.
Girard, Luc
Liu, Hui
Rodriguez-Canales, Jaime
Frenkel, Eugene P.
Wistuba, Ignacio I.
Minna, John D.
Hofmann, Sandra L.
Title Systematic siRNA screen unmasks NSCLC growth dependence by palmitoyltransferase DHHC5
Journal name Molecular Cancer Research   Check publisher's open access policy
ISSN 1557-3125
Publication date 2015-04-01
Sub-type Article (original research)
DOI 10.1158/1541-7786.MCR-14-0608
Open Access Status Not yet assessed
Volume 13
Issue 4
Start page 784
End page 794
Total pages 11
Place of publication Philadelphia, PA United States
Publisher American Association for Cancer Research
Language eng
Abstract Protein S-palmitoylation is a widespread and dynamic posttranslational modification that regulates protein–membrane interactions, protein–protein interactions, and protein stability. A large family of palmitoyl acyl transferases, termed the DHHC family due to the presence of a common catalytic motif, catalyzes S-palmitoylation; the role of these enzymes in cancer is largely unexplored. In this study, an RNAi-based screen targeting all 23 members of the DHHC family was conducted to examine the effects on the growth in non–small cell lung cancer (NSCLC). Interestingly, siRNAs directed against DHHC5 broadly inhibited the growth of multiple NSCLC lines but not normal human bronchial epithelial cell (HBEC) lines. Silencing of DHHC5 by lentivirus-mediated expression of DHHC5 shRNAs dramatically reduced in vitro cell proliferation, colony formation, and cell invasion in a subset of cell lines that were examined in further detail. The phenotypes were restored by transfection of a wild-type DHHC5 plasmid but not by a plasmid expressing a catalytically inactive DHHC5. Tumor xenograft formation was severely inhibited by DHHC5 knockdown and rescued by DHHC5 expression, using both a conventional and tetracycline-inducible shRNA. These data indicate that DHHC5 has oncogenic capacity and contributes to tumor formation in NSCLC, thus representing a potential novel therapeutic target.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Tue, 27 Sep 2016, 20:04:33 EST by Jill Larsen on behalf of School of Medicine