Document detail
ID

doi:10.1038/s41389-022-00435-1...

Author
Kim, Mijeong Singh, Manjot Lee, Bum-Kyu Hibbs, Moira Richardson, Kirsty Ellies, Lesley Wintle, Larissa Stuart, Lisa M. Wang, Jenny Y. Voon, Dominic C. Blancafort, Pilar Wang, Jianlong Kim, Jonghwan Leedman, Peter J. Woo, Andrew J.
Langue
en
Editor

Nature

Category

Medicine & Public Health

Year

2022

listing date

10/12/2022

Keywords
traits stem aggressive migration cancer znf148 myc cell
Metrics

Abstract

The MYC proto-oncogene ( MYC ) is one of the most frequently overexpressed genes in breast cancer that drives cancer stem cell-like traits, resulting in aggressive disease progression and poor prognosis.

In this study, we identified zinc finger transcription factor 148 ( ZNF148 , also called Zfp148 and ZBP-89) as a direct target of MYC.

ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC in breast cancer.

Depletion of ZNF148 by short hairpin RNA (shRNA) and CRISPR/Cas9 increased triple-negative breast cancer (TNBC) cell proliferation and migration.

Global transcriptome and chromatin occupancy analyses of ZNF148 revealed a central role in inhibiting cancer cell de-differentiation and migration.

Mechanistically, we identified the Inhibitor of DNA binding 1 and 3 ( ID1, ID3 ), drivers of cancer stemness and plasticity, as previously uncharacterized targets of transcriptional repression by ZNF148.

Silencing of ZNF148 increased the stemness and tumorigenicity in TNBC cells.

These findings uncover a previously unknown tumor suppressor role for ZNF148, and a transcriptional regulatory circuitry encompassing MYC, ZNF148, and ID1/3 in driving cancer stem cell traits in aggressive breast cancer.

Kim, Mijeong,Singh, Manjot,Lee, Bum-Kyu,Hibbs, Moira,Richardson, Kirsty,Ellies, Lesley,Wintle, Larissa,Stuart, Lisa M.,Wang, Jenny Y.,Voon, Dominic C.,Blancafort, Pilar,Wang, Jianlong,Kim, Jonghwan,Leedman, Peter J.,Woo, Andrew J., 2022, A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer, Nature

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