Creatine kinase B, a downstream effector of c-Myb, controls
migration of osteosarcoma cells via regulation of N-cadherin

J 2026

Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin

POKLUDOVÁ, Jana; Petr LAPČÍK; Iva STANICZKOVÁ ZAMBO; Jiří KOHOUTEK; Danica ZAPLETALOVÁ et al.

Základní údaje

Originální název

Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin

Autoři

Vydání

Cancer Cell International, BIOMED CENTRAL LTD, 2026, 1475-2867

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.000 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1186/s12935-025-04087-0

UT WoS

001660333300003

EID Scopus

2-s2.0-105027398127

Klíčová slova anglicky

Osteosarcoma; c-Myb; Creatine kinase B (CKB); Tumor metastasis; Cell migration

Štítky

14313050, 14314010

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 1. 2026 13:40, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Background We have recently identified transcription factor c-Myb as a negative prognostic factor in osteosarcoma (OSA) patients associated with metastatic disease. Transcriptomic analysis identified creatine kinase B (CKB) as one of the most deregulated genes in OSA cell lines with depleted MYB. CKB is a component of the creatine/phosphocreatine system that plays a key role in maintaining cellular energy homeostasis and energy transport to sites with high demand. This study was therefore conducted to investigate the functional significance of CKB in OSA. Methods Deregulation of CKB by c-Myb in OSA cells was analyzed using gain-of-function/loss-of-function approach. Transactivation of the CKB promoter by c-Myb was assessed using a reporter assay. CRISPR/Cas9, RNAi and cyclocreatine were used to inhibit the expression/activity of CKB in OSA cells. Cell growth, colony-forming capacity, cell migration, chemosensitivity in vitro and metastatic capacity in vivo was examined. CKB protein effectors were identified using liquid chromatography-mass spectrometry (LC-MS) in data-independent acquisition-parallel accumulation serial fragmentation mode. Results CKB was validated as c-Myb target in OSA cell lines. Depletion of CKB using CRISPR/Cas9 resulted in slower migration of OSA cells in vitro and reduced metastatic capacity in immunodeficient mice. siRNA and cyclocreatine inhibited OSA cell migration as well but in this case, cell proliferation was also reduced. A total of 8474 protein groups were quantified, with 147 downregulated and 143 upregulated protein groups associated with the CKB knockout phenotype. The deregulated proteins were enriched for those associated with cell migration and motility. N-cadherin, an established regulator of cell migration, was identified as a target of CKB signaling and its role in OSA cell migration and metastasis was confirmed. Conclusion c-Myb – CKB – N-cadherin axis was identified as pathway regulating OSA cell migration and metastasis.

Návaznosti

EH23_015/0008175, projekt VaV

Název: Inovace České infrastruktury pro integrativní strukturní biologii

GF23-06303K, projekt VaV

Název: Izoforma tropomyosinu Tpm2.3 v regulaci dynamiky aktinu a tvorby metastáz u osteosarkomu

Investor: Grantová agentura ČR, Izoforma tropomyosinu Tpm2.3 v regulaci dynamiky aktinu a tvorby metastáz u osteosarkomu, Lead agentura

LM2023042, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CIISB - Česká infrastruktura pro integrativní strukturní biologii

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

90254, velká výzkumná infrastruktura

Název: e-INFRA CZ II

Přiložené soubory

2538078.pdf

Citovat

POKLUDOVÁ, Jana; Petr LAPČÍK; Iva STANICZKOVÁ ZAMBO; Jiří KOHOUTEK; Danica ZAPLETALOVÁ; Peter MÚDRY; Dagmar ADÁMKOVÁ; Jakub ČERVINKA; Tomáš LOJA; Matej LEXA; Jan VERNER; Jan ŠMARDA; Pavel BOUCHAL; Lucia KNOPFOVÁ a Petr BENEŠ. Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin. Cancer Cell International. BIOMED CENTRAL LTD, 2026, roč. 26, č. 1, s. 1-14. ISSN 1475-2867. Dostupné z: https://doi.org/10.1186/s12935-025-04087-0.

@article{2538078,
   author = {Pokludová, Jana and Lapčík, Petr and Staniczková Zambo, Iva and Kohoutek, Jiří and Zapletalová, Danica and Múdry, Peter and Adámková, Dagmar and Červinka, Jakub and Loja, Tomáš and Lexa, Matej and Verner, Jan and Šmarda, Jan and Bouchal, Pavel and Knopfová, Lucia and Beneš, Petr},
   article_number = {1},
   doi = {https://doi.org/10.1186/s12935-025-04087-0},
   keywords = {Osteosarcoma; c-Myb; Creatine kinase B (CKB); Tumor metastasis; Cell migration},
   language = {eng},
   issn = {1475-2867},
   journal = {Cancer Cell International},
   title = {Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin},
   url = {https://link.springer.com/article/10.1186/s12935-025-04087-0},
   volume = {26},
   year = {2026}
}

TY  - JOUR
ID  - 2538078
AU  - Pokludová, Jana - Lapčík, Petr - Staniczková Zambo, Iva - Kohoutek, Jiří - Zapletalová, Danica - Múdry, Peter - Adámková, Dagmar - Červinka, Jakub - Loja, Tomáš - Lexa, Matej - Verner, Jan - Šmarda, Jan - Bouchal, Pavel - Knopfová, Lucia - Beneš, Petr
PY  - 2026
TI  - Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin
JF  - Cancer Cell International
VL  - 26
IS  - 1
SP  - 1-14
EP  - 1-14
PB  - BIOMED CENTRAL LTD
SN  - 14752867
KW  - Osteosarcoma
KW  - c-Myb
KW  - Creatine kinase B (CKB)
KW  - Tumor metastasis
KW  - Cell migration
UR  - https://link.springer.com/article/10.1186/s12935-025-04087-0
N2  - Background We have recently identified transcription factor c-Myb as a negative prognostic factor in osteosarcoma (OSA) patients associated with metastatic disease. Transcriptomic analysis identified creatine kinase B (CKB) as one of the most deregulated genes in OSA cell lines with depleted MYB. CKB is a component of the creatine/phosphocreatine system that plays a key role in maintaining cellular energy homeostasis and energy transport to sites with high demand. This study was therefore conducted to investigate the functional significance of CKB in OSA. Methods Deregulation of CKB by c-Myb in OSA cells was analyzed using gain-of-function/loss-of-function approach. Transactivation of the CKB promoter by c-Myb was assessed using a reporter assay. CRISPR/Cas9, RNAi and cyclocreatine were used to inhibit the expression/activity of CKB in OSA cells. Cell growth, colony-forming capacity, cell migration, chemosensitivity in vitro and metastatic capacity in vivo was examined. CKB protein effectors were identified using liquid chromatography-mass spectrometry (LC-MS) in data-independent acquisition-parallel accumulation serial fragmentation mode. Results CKB was validated as c-Myb target in OSA cell lines. Depletion of CKB using CRISPR/Cas9 resulted in slower migration of OSA cells in vitro and reduced metastatic capacity in immunodeficient mice. siRNA and cyclocreatine inhibited OSA cell migration as well but in this case, cell proliferation was also reduced. A total of 8474 protein groups were quantified, with 147 downregulated and 143 upregulated protein groups associated with the CKB knockout phenotype. The deregulated proteins were enriched for those associated with cell migration and motility. N-cadherin, an established regulator of cell migration, was identified as a target of CKB signaling and its role in OSA cell migration and metastasis was confirmed. Conclusion c-Myb – CKB – N-cadherin axis was identified as pathway regulating OSA cell migration and metastasis.
ER  -

POKLUDOVÁ, Jana; Petr LAPČÍK; Iva STANICZKOVÁ ZAMBO; Jiří KOHOUTEK; Danica ZAPLETALOVÁ; Peter MÚDRY; Dagmar ADÁMKOVÁ; Jakub ČERVINKA; Tomáš LOJA; Matej LEXA; Jan VERNER; Jan ŠMARDA; Pavel BOUCHAL; Lucia KNOPFOVÁ a Petr BENEŠ. Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin. \textit{Cancer Cell International}. BIOMED CENTRAL LTD, 2026, roč.~26, č.~1, s.~1-14. ISSN~1475-2867. Dostupné z: https://doi.org/10.1186/s12935-025-04087-0.

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