Phosphorylation of Endothelin-Converting Enzyme-1c at Serines 18 and 20 by CK2 Promotes Aggressiveness Traits in Colorectal Cancer Cells

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dc.contributor.authorPérez-Moreno, P.
dc.contributor.authorQuezada-Meza, C.
dc.contributor.authorChavez-Almarza, C.
dc.contributor.authorNiechi, I.
dc.contributor.authorSilva-Pavez, E.
dc.contributor.authorTrigo-Hidalgo, C.
dc.contributor.authorAguayo, F.
dc.contributor.authorJara, L.
dc.contributor.authorCáceres-Verschae, A.
dc.contributor.authorVaras-Godoy, M.
dc.contributor.authorDíaz, V.M.
dc.contributor.authorGarcía de Herreros, A.
dc.date.accessioned2021-09-18T01:15:48Z
dc.date.available2021-09-18T01:15:48Z
dc.date.issued2020-07
dc.descriptionIndexación: Scopus.es
dc.description.abstractEndothelin-converting enzyme-1 (ECE1) activates the endothelin-1 peptide, which upregulates pathways that are related to diverse hallmarks of cancer. ECE1 is expressed as four isoforms differing in their N-terminal domains. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE1c, enhancing its stability and promoting invasiveness of colorectal cancer cells. However, the specific residues in ECE1c that are phosphorylated by CK2 and how this phosphorylation promotes invasiveness was unknown. Here we demonstrate that Ser-18 and Ser-20 are the bona fide residues phosphorylated by CK2 in ECE1c. Thus, biphospho-mimetic ECE1cDD and biphospho-resistant ECE1cAA mutants were constructed and stably expressed in different colorectal cancer cells through lentiviral transduction. Biphospho-mimetic ECE1cDD displayed the highest stability in cells, even in the presence of the specific CK2 inhibitor silmitasertib. Concordantly, ECE1cDD-expressing cells showed enhanced hallmarks of cancer, such as proliferation, migration, invasiveness, and self-renewal capacities. Conversely, cells expressing the less-stable biphospho-resistant ECE1cAA showed a reduction in these features, but also displayed an important sensitization to 5-fluorouracil, an antineoplastic agent traditionally used as therapy in colorectal cancer patients. Altogether, these findings suggest that phosphorylation of ECE1c at Ser-18 and Ser-20 by CK2 promotes aggressiveness in colorectal cancer cells. Therefore, phospho-ECE1c may constitute a novel biomarker of poor prognosis and CK2 inhibition may be envisioned as a potential therapy for colorectal cancer patients. © Copyright © 2020 Pérez-Moreno, Quezada-Meza, Chavez-Almarza, Niechi, Silva-Pavez, Trigo-Hidalgo, Aguayo, Jara, Cáceres-Verschae, Varas-Godoy, Díaz, García de Herreros, Burzio and Tapia.es
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fonc.2020.01004/full
dc.identifier.citationFrontiers in Oncology Open Access Volume 1030 July 2020 Article number 1004es
dc.identifier.doi10.3389/fonc.2020.01004
dc.identifier.issn2234-943X
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/20296
dc.language.isoenes
dc.publisherFrontiers Media S.A.es
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectaggressivenesses
dc.subjectbiomarkeres
dc.subjectcancer prognosises
dc.subjectpharmacological inhibitores
dc.subjectphosphorylationes
dc.subjectprotein stabilityes
dc.titlePhosphorylation of Endothelin-Converting Enzyme-1c at Serines 18 and 20 by CK2 Promotes Aggressiveness Traits in Colorectal Cancer Cellses
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