Unbalanced expression of CK2 kinase subunits is sufficient to drive epithelial-to-mesenchymal transition by Snail1 induction

Autor: Claude Cochet, Yohann Couté, Odile Filhol, Colette Charpin, Sophie Giusiano, E Duchemin-Pelletier, Ivan Mikaelian, Alexandre Deshiere, Yves Vandenbrouck, Delphine Ciais, Florence Combes, E Spreux
Přispěvatelé: Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Registre Multicentrique à Vocation Nationale des Mésothéliomes Pleuraux (MESONAT), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Invasion mechanisms in angiogenesis and cancer (IMAC), Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'étude de la dynamique des protéomes (LEDyP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Cancer Research
Epithelial-Mesenchymal Transition
Protein subunit
[SDV]Life Sciences [q-bio]
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
Bioinformatics
Models
Biological
Gene Expression Regulation
Enzymologic
03 medical and health sciences
0302 clinical medicine
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Genetics
Humans
Epithelial–mesenchymal transition
Casein Kinase II
Protein kinase A
Molecular Biology
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Regulation of gene expression
0303 health sciences
Kinase
Microarray analysis techniques
Gene Expression Profiling
Carcinoma
Microarray Analysis
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Up-Regulation
Cell biology
Gene Expression Regulation
Neoplastic
Isoenzymes
Gene expression profiling
Protein Subunits
Tissue Array Analysis
030220 oncology & carcinogenesis
embryonic structures
Phosphorylation
Female
Snail Family Transcription Factors
Transcription Factors
Zdroj: Oncogene
Oncogene, Nature Publishing Group, 2013, 32 (11), pp.1373-1383. ⟨10.1038/onc.2012.165⟩
Oncogene, 2013, 32 (11), pp.1373-1383. ⟨10.1038/onc.2012.165⟩
ISSN: 0950-9232
1476-5594
DOI: 10.1038/onc.2012.165⟩
Popis: Epithelial-to-mesenchymal transition (EMT) is closely linked to conversion of early-stage tumours into invasive malignancies. Many signalling pathways are involved in EMT, but the key regulatory kinases in this important process have not been clearly identified. Protein kinase CK2 is a multi-subunit protein kinase, which, when overexpressed, has been linked to disease progression and poor prognosis in various cancers. Specifically, overexpression of CK2α in human breast cancers is correlated with metastatic risk. In this article, we show that an imbalance of CK2 subunits reflected by a decrease in the CK2β regulatory subunit in a subset of breast tumour samples is correlated with induction of EMT-related markers. CK2β-depleted epithelial cells displayed EMT-like morphological changes, enhanced migration, and anchorage-independent growth, all of which require Snail1 induction. In epithelial cells, Snail1 stability is negatively regulated by CK2 and GSK3β through synergistic hierarchal phosphorylation. This process depends strongly on CK2β, thus confirming that CK2 functions upstream of Snail1. In primary breast tumours, CK2β underexpression also correlates strongly with expression of EMT markers, emphasizing the link between asymmetric expression of CK2 subunits and EMT in vivo. Our results therefore highlight the importance of CK2β in controlling epithelial cell plasticity. They show that CK2 holoenzyme activity is essential to suppress EMT, and that it contributes to maintaining a normal epithelial morphology. This study also suggests that unbalanced expression of CK2 subunits may drive EMT, thereby contributing to tumour progression.
Databáze: OpenAIRE
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