2. Academic Validation
  3. RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer

RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer

  • EMBO Rep. 2024 Oct 17. doi: 10.1038/s44319-024-00282-8.
Yutaro Uchida 1,  Ryota Kurimoto 1,  Tomoki Chiba 1,  Takahide Matsushima 1,  Goshi Oda 2,  Iichiroh Onishi 3,  Yasuto Takeuchi 4 5,  Noriko Gotoh 4 5,  Hiroshi Asahara 6 7
Affiliations

Affiliations

  • 1 Department of Systems Biomedicine, Institute of Science Tokyo, Tokyo, 113-8510, Japan.
  • 2 Department of Surgery, Breast Surgery, Institute of Science Tokyo, Tokyo, 113-8510, Japan.
  • 3 Department of Comprehensive Pathology, Institute of Science Tokyo, Tokyo, 113-8510, Japan.
  • 4 Division of Cancer Cell Biology, Kanazawa University, Kanazawa, 920-1192, Japan.
  • 5 Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, 920-1192, Japan.
  • 6 Department of Systems Biomedicine, Institute of Science Tokyo, Tokyo, 113-8510, Japan. asahara.syst@tmd.ac.jp.
  • 7 Department of Molecular and Cellular Biology, Scripps Research, La Jolla, CA, 92037, USA. asahara.syst@tmd.ac.jp.
PMID: 39420119 DOI: 10.1038/s44319-024-00282-8
Abstract

Triple-negative breast Cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the Cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element "UGUWHWWA" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of Cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts.

Keywords

Breast Cancer; Cancer Stem Cells; RNA Binding Protein; ZEB1; mRNA Stabilization.

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