Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth.

CP: Cancer CP: Molecular biology DDX4 RNA regulation RNP granules cancer cancer-germline antigens tumor growth

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
03 Jul 2024
Historique:
received: 12 11 2023
revised: 15 05 2024
accepted: 18 06 2024
medline: 4 7 2024
pubmed: 4 7 2024
entrez: 4 7 2024
Statut: aheadofprint

Résumé

Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.

Identifiants

DOI: 10.1016/j.celrep.2024.114430 PMID: 38963760
pubmed: 38963760
pii: S2211-1247(24)00759-9
doi: 10.1016/j.celrep.2024.114430
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114430

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Opeyemi Olotu (O)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Anna-Riina Koskenniemi (AR)

Department of Pathology, Laboratory Division, Turku University Hospital and University of Turku, 20520 Turku, Finland.

Lin Ma (L)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Valeriy Paramonov (V)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20500 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.

Sini Laasanen (S)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Elina Louramo (E)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Matthieu Bourgery (M)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Centre for Population Health Research, Turku University Hospital and University of Turku, 20520 Turku, Finland.

Tiina Lehtiniemi (T)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Samuli Laasanen (S)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Adolfo Rivero-Müller (A)

Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland.

Eliisa Löyttyniemi (E)

Department of Biostatistics, University of Turku and Turku University Hospital, 20520 Turku, Finland.

Cecilia Sahlgren (C)

Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20500 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.

Jukka Westermarck (J)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.

Sami Ventelä (S)

Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Department for Otorhinolaryngology, Head, and Neck Surgery, University of Turku and Turku University Hospital, 20520 Turku, Finland.

Tapio Visakorpi (T)

Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, 33520 Tampere, Finland; Fimlab Laboratories, Tampere University Hospital, 33520 Tampere, Finland.

Matti Poutanen (M)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Turku Center for Disease Modeling, University of Turku, 20520 Turku, Finland; FICAN West Cancer Center, University of Turku, Turku University Hospital, 20500 Turku, Finland.

Paula Vainio (P)

Department of Pathology, Laboratory Division, Turku University Hospital and University of Turku, 20520 Turku, Finland.

Juho-Antti Mäkelä (JA)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.

Noora Kotaja (N)

Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland. Electronic address: noora.kotaja@utu.fi.

Classifications MeSH