WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer.

Cell Death & Disease
Ayse ErtayYihua Wang

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clini...Continue Reading

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Methods Mentioned

BETA
transfections
flow cytometry
light microscopy
fluorescence-activated cell sorting
transfection
immunoprecipitations

Software Mentioned

ToppGene
ImageJ
cellHTS
SPSS
PEPROTECH
RStudio
GraphPad Prism
ToppGene Suite

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