Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth
Olotu, Opeyemi; Koskenniemi, Anna Riina; Ma, Lin; Paramonov, Valeriy; Laasanen, Sini; Louramo, Elina; Bourgery, Matthieu; Lehtiniemi, Tiina; Laasanen, Samuli; Rivero-Müller, Adolfo; Löyttyniemi, Eliisa; Sahlgren, Cecilia; Westermarck, Jukka; Ventelä, Sami; Visakorpi, Tapio; Poutanen, Matti; Vainio, Paula; Mäkelä, Juho Antti; Kotaja, Noora (2024-07-23)
Olotu, Opeyemi
Koskenniemi, Anna Riina
Ma, Lin
Paramonov, Valeriy
Laasanen, Sini
Louramo, Elina
Bourgery, Matthieu
Lehtiniemi, Tiina
Laasanen, Samuli
Rivero-Müller, Adolfo
Löyttyniemi, Eliisa
Sahlgren, Cecilia
Westermarck, Jukka
Ventelä, Sami
Visakorpi, Tapio
Poutanen, Matti
Vainio, Paula
Mäkelä, Juho Antti
Kotaja, Noora
23.07.2024
114430
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202407177654
https://urn.fi/URN:NBN:fi:tuni-202407177654
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [19236]