Expression of oncogenic drivers in 3D cell culture depends on nuclear ATP synthesis by NUDT5
Autor/a
Pickup, Katherine E.
Pardow, Felicitas
Carbonell-Caballero, José
Lioutas, Antonios
Villanueva-Cañas, José Luis
Wright, Roni H.G.
Beato, Miguel
Data de publicació
2019ISSN
2072-6694
Resum
The growth of cancer cells as oncospheres in three-dimensional (3D) culture provides a robust cell model for understanding cancer progression, as well as for early drug discovery and validation. We have previously described a novel pathway in breast cancer cells, whereby ADP (Adenosine diphosphate)-ribose derived from hydrolysis of poly (ADP-Ribose) and pyrophosphate (PPi) are converted to ATP, catalysed by the enzyme NUDT5 (nucleotide diphosphate hydrolase type 5). Overexpression of the NUDT5 gene in breast and other cancer types is associated with poor prognosis, increased risk of recurrence and metastasis. In order to understand the role of NUDT5 in cancer cell growth, we performed phenotypic and global expression analysis in breast cancer cells grown as oncospheres. Comparison of two-dimensional (2D) versus 3D cancer cell cultures from different tissues of origin suggest that NUDT5 increases the aggressiveness of the disease via the modulation of several key driver genes, including ubiquitin specific peptidase 22 (USP22), RAB35B, focadhesin (FOCAD) and prostagladin E synthase (PTGES). NUDT5 functions as a master regulator of key oncogenic pathways and of genes involved in cell adhesion, cancer stem cell (CSC) maintenance and epithelial to mesenchyme transition (EMT). Inhibiting the enzymatic activities of NUDT5 prevents oncosphere formation and precludes the activation of cancer driver genes. These findings highlight NUDT5 as an upstream regulator of tumour drivers and may provide a biomarker for cancer stratification, as well as a novel target for drug discovery for combinatorial drug regimens for the treatment of aggressive cancer types and metastasis.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
Anglès
Matèries (CDU)
61 - Medicina
616 - Patologia. Medicina clínica. Oncologia
Paraules clau
Càncer de pulmó
Proliferació
Oncosferes
Comunicació cèl·lula-cèl·lula
Citoesquelet
Motilitat
Recurrència
Cèl·lules mare cancerígenes
Metàstasi
Cultius cel·lulars
Cáncer de pulmón
Proliferación
Oncosferas
Comunicación célula-célula
Citoesqueleto
Motilidad
Recurrencia
Células madre cancerígenas
Metástasis
Cultivos celulares
Lung cancer
Proliferation
Oncospheres
Cell-cell communication
Cytoskeleton
Motility
Recurrence
Carcinogenic stem cells
Metastasis
Cell cultures
Pàgines
17
Publicat per
MDPI
Col·lecció
11;9
Publicat a
Cancers
Citació
Pickup, Katherine E.; Pardow, Felicitas; Carbonell-Caballero, José [et al.]. Expression of oncogenic drivers in 3D cell culture depends on nuclear ATP synthesis by NUDT5. Cancers, 2019, 11(9), 1337. Disponible en: <https://www.mdpi.com/2072-6694/11/9/1337>. Fecha de acceso: 14 dic. 2021. DOI: 10.3390/cancers11091337
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- Ciències de la Salut [725]
Drets
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