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dc.contributor.author
Silva Pavez, Eduardo  
dc.contributor.author
Villar, Paulina  
dc.contributor.author
Trigo, César  
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Caamaño, Esteban  
dc.contributor.author
Niechi, Ignacio  
dc.contributor.author
Pérez, Pablo  
dc.contributor.author
Muñoz, Juan Pablo  
dc.contributor.author
Aguayo, Francisco  
dc.contributor.author
Burzio, Verónica A.  
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Varas Godoy, Manuel  
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Castro, Ariel F.  
dc.contributor.author
Colombo, Maria Isabel  
dc.contributor.author
Tapia, Julio C.  
dc.date.available
2021-01-28T02:58:37Z  
dc.date.issued
2019-02  
dc.identifier.citation
Silva Pavez, Eduardo; Villar, Paulina; Trigo, César; Caamaño, Esteban; Niechi, Ignacio; et al.; CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells; Nature Publishing Group; Cell Death and Disease; 10; 2; 2-2019; 1-13  
dc.identifier.issn
2041-4889  
dc.identifier.uri
http://hdl.handle.net/11336/123990  
dc.description.abstract
Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal cancer (CRC) patients. On the other hand, mTORC1 plays an important role in the regulation of protein synthesis, cell growth, and autophagy. Some studies suggest that CK2 regulates mTORC1 in several cancers. The most recently developed CK2 inhibitor, silmitasertib (formerly CX-4945), has been tested in phase I/II trials for cholangiocarcinoma and multiple myeloma. This drug has been shown to induce autophagy and enhance apoptosis in pancreatic cancer cells and to promote apoptosis in non-small cell lung cancer cells. Nevertheless, it has not been tested in studies for CRC patients. We show in this work that inhibition of CK2 with silmitasertib decreases in vitro tumorigenesis of CRC cells in response to G2/M arrest, which correlates with mTORC1 inhibition and formation of large cytoplasmic vacuoles. Notably, molecular markers indicate that these vacuoles derive from massive macropinocytosis. Altogether, these findings suggest that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/  
dc.subject
CANCER  
dc.subject
CK2  
dc.subject
MTORC1  
dc.subject
AUTOPHAGY  
dc.subject.classification
Bioquímica y Biología Molecular  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2020-11-19T22:02:46Z  
dc.journal.volume
10  
dc.journal.number
2  
dc.journal.pagination
1-13  
dc.journal.pais
Reino Unido  
dc.description.fil
Fil: Silva Pavez, Eduardo. Universidad de Chile; Chile  
dc.description.fil
Fil: Villar, Paulina. Universidad de Chile; Chile  
dc.description.fil
Fil: Trigo, César. Universidad de Chile; Chile  
dc.description.fil
Fil: Caamaño, Esteban. Universidad de Chile; Chile  
dc.description.fil
Fil: Niechi, Ignacio. Universidad de Chile; Chile. Universidad Austral de Chile; Chile  
dc.description.fil
Fil: Pérez, Pablo. Universidad de Chile; Chile  
dc.description.fil
Fil: Muñoz, Juan Pablo. Universidad de Chile; Chile  
dc.description.fil
Fil: Aguayo, Francisco. Universidad de Chile; Chile  
dc.description.fil
Fil: Burzio, Verónica A.. Universidad Andrés Bello; Chile  
dc.description.fil
Fil: Varas Godoy, Manuel. Universidad de Los Andes; Chile  
dc.description.fil
Fil: Castro, Ariel F.. Universidad de Concepción; Chile  
dc.description.fil
Fil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina  
dc.description.fil
Fil: Tapia, Julio C.. Universidad de Chile; Chile  
dc.journal.title
Cell Death and Disease  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41419-019-1306-x  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41419-019-1306-x