J 2022

Transcription factor c-Myb: novel prognostic factor in osteosarcoma

ŘÍHOVÁ, Kamila; Monika DÚCKA; Iva STANICZKOVÁ ZAMBO; Ladislava VYMĚTALOVÁ; Martin ŠRÁMEK et. al.

Základní údaje

Originální název

Transcription factor c-Myb: novel prognostic factor in osteosarcoma

Autoři

ŘÍHOVÁ, Kamila ORCID; Monika DÚCKA; Iva STANICZKOVÁ ZAMBO; Ladislava VYMĚTALOVÁ; Martin ŠRÁMEK; Filip TRČKA; Jan VERNER ORCID; Stanislav DRÁPELA; Radek FEDR; Tereza SUCHÁNKOVÁ; Barbora PAVLATOVSKÁ; Eva ONDROUŠKOVÁ; Irena KUBELKOVÁ; Danica ZAPLETALOVÁ; Štěpán TUČEK; Peter MÚDRY; Dagmar ADÁMKOVÁ KRÁKOROVÁ; Lucia KNOPFOVÁ; Jan ŠMARDA; Karel SOUČEK; Lubor BORSIG a Petr BENEŠ

Vydání

Clinical & Experimental Metastasis, Springer, 2022, 0262-0898

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 4.000

Kód RIV

RIV/00216224:14310/22:00125156

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000740192800001

EID Scopus

2-s2.0-85122517430

Klíčová slova anglicky

c-Myb; Chemoresistance; Metastasis; Osteosarcoma; Prognosis; Proliferation

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 25. 5. 2022 10:05, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.

Návaznosti

NV18-07-00073, projekt VaV
Název: c-Myb a jeho transkripční program ve fyziologických a patologických osteogenních procesech
Investor: Ministerstvo zdravotnictví ČR, c-Myb a jeho transkripční program ve fyziologických a patologických osteogenních procesech