XPO1 blockade with KPT-330 promotes apoptosis in cutaneous T-cell lymphoma by activating the p53-p21 and p27 pathways.

Humans Exportin 1 Protein Receptors, Cytoplasmic and Nuclear / metabolism Lymphoma, T-Cell, Cutaneous / drug therapy Apoptosis / drug effects Animals Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / metabolism Tumor Suppressor Protein p53 / metabolism Karyopherins / metabolism Mice Cell Line, Tumor Triazoles / pharmacology Cell Proliferation / drug effects Hydrazines / pharmacology Xenograft Model Antitumor Assays Signal Transduction / drug effects Gene Expression Regulation, Neoplastic / drug effects

Journal

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

Informations de publication

Date de publication:
23 04 2024
Historique:
received: 18 09 2023
accepted: 17 04 2024
medline: 24 4 2024
pubmed: 24 4 2024
entrez: 23 4 2024
Statut: epublish

Résumé

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in CTCL cells. KPT-330 reduces cell proliferation, induces G1 cell cycle arrest and apoptosis. RNA-sequencing was used to explore the underlying mechanisms. Genes associated with the cell cycle and the p53 pathway were significantly enriched with KPT-330 treatment. KPT-330 suppressed XPO1 expression, upregulated p53, p21

Identifiants

DOI: 10.1038/s41598-024-59994-5 PMID: 38653804
pubmed: 38653804
doi: 10.1038/s41598-024-59994-5
pii: 10.1038/s41598-024-59994-5
doi:

Substances chimiques

Exportin 1 Protein 0
Receptors, Cytoplasmic and Nuclear 0
Cyclin-Dependent Kinase Inhibitor p21 0
Cyclin-Dependent Kinase Inhibitor p27 147604-94-2
Tumor Suppressor Protein p53 0
selinexor 31TZ62FO8F
Karyopherins 0
Triazoles 0
Hydrazines 0
CDKN1A protein, human 0
TP53 protein, human 0
CDKN1B protein, human 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

9305

Informations de copyright

© 2024. The Author(s).

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Auteurs

Nitin Chakravarti (N)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, BLSB 328, Philadelphia, PA, 19107, USA. nitin.chakravarti@jefferson.edu.

Amy Boles (A)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Rachel Burzinski (R)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Paola Sindaco (P)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Colleen Isabelle (C)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Kathleen McConnell (K)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Anjali Mishra (A)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Pierluigi Porcu (P)

Division of Hematologic Malignancies, Sidney Kimmel Cancer Center, Thomas Jefferson University, 834 Chestnut Street, Suite 320, Philadelphia, PA, 19107, USA. pierluigi.porcu@jefferson.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome T › Lymphome T cutané › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Eucaryotes › Animaux › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › Inhibiteur p21 de kinase cycline-dépendante › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéines inhibitrices des kinases cyclines-dépendantes › Inhibiteur p27 de kinase cycline-dépendante › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Caryophérines › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Triazoles › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Composés chimiques organiques › Hydrazines › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › XPO1 blockade with KPT-330 promotes apoptosis...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › XPO1 blockade with KPT-330 promotes apoptosis...