Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway.

Cell Line, Tumor Cell Proliferation / genetics Forkhead Box Protein M1 / genetics Gene Expression Regulation, Neoplastic Humans Intracellular Signaling Peptides and Proteins / metabolism Kinesins / genetics Microtubule-Associated Proteins / genetics Triple Negative Breast Neoplasms / metabolism Wnt Signaling Pathway beta Catenin / metabolism
FOXM1 H3K4me3 KIF23 Triple negative breast cancer WDR5 Wnt/β-catenin pathway

Journal

Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647

Informations de publication

Date de publication:
07 May 2022
Historique:
received: 06 01 2022
accepted: 25 04 2022
entrez: 7 5 2022
pubmed: 8 5 2022
medline: 11 5 2022
Statut: epublish

Résumé

Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. KIF23 plays a crucial role in the tumorigenesis and cancer progression. However, the role of KIF23 in development of TNBC and the underlying mechanism remain unknown. The study aimed to elucidate the biological function and regulatory mechanism of KIF23 in TNBC. Quantitative real-time PCR and Western blot were used to determine the KIF23 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of KIF23 on tumor growth and metastasis in TNBC. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of KIF23 in TNBC. We found that KIF23 was significantly up-regulated and associated with poor prognosis in TNBC. KIF23 could promote TNBC proliferation, migration and invasion in vitro and in vivo. KIF23 could activate Wnt/β-catenin pathway and promote EMT progression in TNBC. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of KIF23 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. Our findings elucidate WDR5/FOXM1/KIF23/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

Sections du résumé

BACKGROUND BACKGROUND
Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. KIF23 plays a crucial role in the tumorigenesis and cancer progression. However, the role of KIF23 in development of TNBC and the underlying mechanism remain unknown. The study aimed to elucidate the biological function and regulatory mechanism of KIF23 in TNBC.
METHODS METHODS
Quantitative real-time PCR and Western blot were used to determine the KIF23 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of KIF23 on tumor growth and metastasis in TNBC. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of KIF23 in TNBC.
RESULTS RESULTS
We found that KIF23 was significantly up-regulated and associated with poor prognosis in TNBC. KIF23 could promote TNBC proliferation, migration and invasion in vitro and in vivo. KIF23 could activate Wnt/β-catenin pathway and promote EMT progression in TNBC. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of KIF23 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression.
CONCLUSIONS CONCLUSIONS
Our findings elucidate WDR5/FOXM1/KIF23/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

Identifiants

DOI: 10.1186/s13046-022-02373-7 PMID: 35524313 PMC: PMC9077852
pubmed: 35524313
doi: 10.1186/s13046-022-02373-7
pii: 10.1186/s13046-022-02373-7
pmc: PMC9077852
doi:

Substances chimiques

FOXM1 protein, human 0
Forkhead Box Protein M1 0
Intracellular Signaling Peptides and Proteins 0
KIF23 protein, human 0
Microtubule-Associated Proteins 0
WDR5 protein, human 0
beta Catenin 0
Kinesins EC 3.6.4.4

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

168

Subventions

Organisme : National Natural Science Foundation of China
ID : 81972486
Organisme : National Natural Science Foundation of China
ID : 81802748
Organisme : National Natural Science Foundation of China
ID : 81802644
Organisme : the Key Medical Talents of Jiangsu Province
ID : ZDRCA2016029
Organisme : '333' High-level Talents Training Project of Jiangsu Province
ID : BRA2016505
Organisme : he International Cooperation Project of Jiangsu Provincial Science and Technology Department
ID : BZ2018054
Organisme : the Priority Academic Program Development of Jiangsu Higher Education Institutions
ID : JX10231801

Informations de copyright

© 2022. The Author(s).

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Auteurs

Zhi Li (Z)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.
Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

Hai-Yan Yang (HY)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.

Xiao-Lan Zhang (XL)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.
Department of Breast Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, #68 Gehu Middle Road, Wujin District, Changzhou, 213000, Jiangsu, China.

Xu Zhang (X)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.

Yu-Zhou Huang (YZ)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.

Xin-Yuan Dai (XY)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.

Liang Shi (L)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China.

Guo-Ren Zhou (GR)

Department of Oncology, Jiangsu Cancer Hospital & the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, 210009, PR China. zhouguoren888@njmu.edu.cn.

Ji-Fu Wei (JF)

Department of Pharmacy, Jiangsu Cancer Hospital & the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, 210009, PR China. weijifu@njmu.edu.cn.
Research Division of Clinical Pharmacology, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China. weijifu@njmu.edu.cn.

Qiang Ding (Q)

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, PR China. dingqiang@njmu.edu.cn.
ORCID: 0000-0003-1499-6200

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › Protéine M1 à motif en tête de fourche › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Kinésine › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Tumeurs du sein triple-négatives › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Kinesin family member 23, regulated by FOXM1,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Kinesin family member 23, regulated by FOXM1,...