Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis.

Animals Antineoplastic Agents / pharmacology Breast Neoplasms / drug therapy Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects ELAV-Like Protein 1 / antagonists & inhibitors Female Forkhead Transcription Factors / genetics Humans Lung Neoplasms / genetics Mice, Inbred BALB C Mice, Nude Middle Aged Neoplasm Invasiveness Signal Transduction Tumor Burden / drug effects Xenograft Model Antitumor Assays

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
24 04 2020
Historique:
received: 24 04 2019
accepted: 07 04 2020
entrez: 26 4 2020
pubmed: 26 4 2020
medline: 16 6 2021
Statut: epublish

Résumé

Patients diagnosed with metastatic breast cancer have a dismal 5-year survival rate of only 24%. The RNA-binding protein Hu antigen R (HuR) is upregulated in breast cancer, and elevated cytoplasmic HuR correlates with high-grade tumors and poor clinical outcome of breast cancer. HuR promotes tumorigenesis by regulating numerous proto-oncogenes, growth factors, and cytokines that support major tumor hallmarks including invasion and metastasis. Here, we report a HuR inhibitor KH-3, which potently suppresses breast cancer cell growth and invasion. Furthermore, KH-3 inhibits breast cancer experimental lung metastasis, improves mouse survival, and reduces orthotopic tumor growth. Mechanistically, we identify FOXQ1 as a direct target of HuR. KH-3 disrupts HuR-FOXQ1 mRNA interaction, leading to inhibition of breast cancer invasion. Our study suggests that inhibiting HuR is a promising therapeutic strategy for lethal metastatic breast cancer.

Identifiants

DOI: 10.1038/s42003-020-0933-1 PMID: 32332873 PMC: PMC7181695
pubmed: 32332873
doi: 10.1038/s42003-020-0933-1
pii: 10.1038/s42003-020-0933-1
pmc: PMC7181695
doi:

Substances chimiques

Antineoplastic Agents 0
ELAV-Like Protein 1 0
ELAVL1 protein, human 0
FOXQ1 protein, human 0
Forkhead Transcription Factors 0

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

193

Subventions

Organisme : NIGMS NIH HHS
ID : P20 GM103638
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA168524
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA191785
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA243445
Pays : United States

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Auteurs

Xiaoqing Wu (X)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.
ORCID: 0000-0003-2076-4107

Gulhumay Gardashova (G)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
ORCID: 0000-0002-2567-1893

Lan Lan (L)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
ORCID: 0000-0002-8045-7654

Shuang Han (S)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.

Cuncong Zhong (C)

Department of Electrical Engineering and Computer Science, The University of Kansas, Lawrence, KS, USA.
ORCID: 0000-0002-8777-082X

Rebecca T Marquez (RT)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.

Lanjing Wei (L)

Bioengineering Program, The University of Kansas, Lawrence, KS, USA.

Spencer Wood (S)

Department of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.

Sudeshna Roy (S)

Department of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.
ORCID: 0000-0003-0237-4156

Ragul Gowthaman (R)

Center for Computational Biology, The University of Kansas, Lawrence, KS, USA.
ORCID: 0000-0002-0008-6401

John Karanicolas (J)

Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA, USA.
ORCID: 0000-0003-0300-726X

Fei P Gao (FP)

Protein Production Group, NIH COBRE in Protein Structure and Function, The University of Kansas, Lawrence, KS, USA.
ORCID: 0000-0001-9741-9390

Dan A Dixon (DA)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.
ORCID: 0000-0001-5631-4365

Danny R Welch (DR)

The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.
Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, KS, USA.
ORCID: 0000-0002-1951-4947

Ling Li (L)

National Translational Science Center for Molecular Medicine, Department of Cell Biology, School of Basic Medicine, The Air Force Medical University, Xi'an, Shanxi, China.

Min Ji (M)

School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China.
ORCID: 0000-0002-8468-7772

Jeffrey Aubé (J)

Department of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
ORCID: 0000-0003-1049-5767

Liang Xu (L)

Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA. xul@ku.edu.
The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA. xul@ku.edu.
Department of Radiation Oncology, The University of Kansas Medical Center, Kansas City, KS, USA. xul@ku.edu.
ORCID: 0000-0001-9196-4232

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Protéines à motif de reconnaissance de l'ARN › Antigènes Hu de l'encéphalomyélite paranéoplasique › Protéine-1 similaire à ELAV › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Targeting the interaction between RNA-binding...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Invasion tumorale › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Techniques d'investigation › Charge tumorale › Targeting the interaction between RNA-binding...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Targeting the interaction between RNA-binding...