Doublecortin-like kinase 1 promotes hepatocyte clonogenicity and oncogenic programming via non-canonical β-catenin-dependent mechanism.

Animals Carcinogenesis Carcinoma, Hepatocellular / genetics Cell Line, Tumor Doublecortin-Like Kinases Glycogen Synthase Kinase 3 beta / metabolism Hep G2 Cells Hepatocytes / cytology Heterografts Humans Intracellular Signaling Peptides and Proteins / metabolism Liver Cirrhosis / pathology Liver Neoplasms / genetics Mice Mice, Inbred C57BL Neoplastic Stem Cells / metabolism Protein Serine-Threonine Kinases / metabolism SOX9 Transcription Factor / metabolism Spheroids, Cellular alpha-Fetoproteins / metabolism beta Catenin / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
29 06 2020
Historique:
received: 18 03 2019
accepted: 03 06 2020
entrez: 1 7 2020
pubmed: 1 7 2020
medline: 16 1 2021
Statut: epublish

Résumé

Chronic liver injury is a risk factor for cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms that regulate the decision between normal injury repair and neoplastic initiation are unclear. Doublecortin-like kinase 1 (DCLK1), a tumor stem cell marker, is induced during cirrhosis and HCC. Here, we demonstrate that DCLK1-overexpressing primary human hepatocytes formed spheroids in suspension cultures. Spheroids derived from DCLK1-overexpressing hepatoma cells showed high level expression of active β-catenin, α-fetoprotein, and SOX9, suggesting that DCLK1 overexpression induces clonogenicity and dedifferentiated phenotypes in hepatoma cells. DCLK1 overexpression in hepatoma cells also increased phosphorylation of GSK-3β at Ser

Identifiants

DOI: 10.1038/s41598-020-67401-y PMID: 32601309 PMC: PMC7324569
pubmed: 32601309
doi: 10.1038/s41598-020-67401-y
pii: 10.1038/s41598-020-67401-y
pmc: PMC7324569
doi:

Substances chimiques

AFP protein, human 0
CTNNB1 protein, human 0
Intracellular Signaling Peptides and Proteins 0
SOX9 Transcription Factor 0
SOX9 protein, human 0
alpha-Fetoproteins 0
beta Catenin 0
DCLK1 protein, human EC 2.7.1.11
Doublecortin-Like Kinases EC 2.7.1.11
Glycogen Synthase Kinase 3 beta EC 2.7.11.1
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

10578

Subventions

Organisme : NIGMS NIH HHS
ID : P20 GM103447
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Organisme : BLRD VA
ID : I01 BX004131
Pays : United States
Organisme : BLRD VA
ID : I01 BX001952
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103639
Pays : United States
Organisme : CSRD VA
ID : I01 CX001686
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA233186
Pays : United States

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Auteurs

Naushad Ali (N)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Naushad-ali@ouhsc.edu.
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA. Naushad-ali@ouhsc.edu.
Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Naushad-ali@ouhsc.edu.

Charles B Nguyen (CB)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Parthasarathy Chandrakesan (P)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.
Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
ORCID: 0000-0002-7587-9553

Roman F Wolf (RF)

Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Dongfeng Qu (D)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.

Randal May (R)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Tatiana Goretsky (T)

Division of Gastroenterology, Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA.

Javid Fazili (J)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Terrence A Barrett (TA)

Division of Gastroenterology, Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA.

Min Li (M)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.

Mark M Huycke (MM)

Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
ORCID: 0000-0002-6110-5629

Michael S Bronze (MS)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Courtney W Houchen (CW)

Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Courtney-houchen@ouhsc.edu.
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA. Courtney-houchen@ouhsc.edu.
Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Courtney-houchen@ouhsc.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Kinases de type doublecortine › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Proline-directed protein kinases › Glycogen Synthase Kinase 3 › Glycogen synthase kinase 3 beta › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › Cellules HepG2 › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Régions du corps › Transplants › Hétérogreffes › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches tumorales › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription SOX › Facteurs de transcription SOX-E › Facteur de transcription SOX-9 › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Cellules › Cellules cultivées › Sphéroïdes de cellules › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Alphafoetoprotéines › Doublecortin-like kinase 1 promotes hepatocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Doublecortin-like kinase 1 promotes hepatocyte...