Transcription factor c-Myb: novel prognostic factor in
osteosarcoma

J 2022

Transcription factor c-Myb: novel prognostic factor in osteosarcoma

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

Basic information

Original name

Transcription factor c-Myb: novel prognostic factor in osteosarcoma

Authors

ŘÍHOVÁ, Kamila (203 Czech Republic, belonging to the institution), Monika DÚCKA (703 Slovakia, belonging to the institution), Iva STANICZKOVÁ ZAMBO (203 Czech Republic, belonging to the institution), Ladislava VYMĚTALOVÁ (203 Czech Republic, belonging to the institution), Martin ŠRÁMEK (203 Czech Republic, belonging to the institution), Filip TRČKA (203 Czech Republic, belonging to the institution), Jan VERNER (203 Czech Republic, belonging to the institution), Stanislav DRÁPELA (203 Czech Republic, belonging to the institution), Radek FEDR (203 Czech Republic), Tereza SUCHÁNKOVÁ, Barbora PAVLATOVSKÁ (203 Czech Republic, belonging to the institution), Eva ONDROUŠKOVÁ (203 Czech Republic, belonging to the institution), Irena KUBELKOVÁ, Danica ZAPLETALOVÁ (703 Slovakia, belonging to the institution), Štěpán TUČEK, Peter MÚDRY (203 Czech Republic, belonging to the institution), Dagmar ADÁMKOVÁ KRÁKOROVÁ, Lucia KNOPFOVÁ (203 Czech Republic, belonging to the institution), Jan ŠMARDA (203 Czech Republic, belonging to the institution), Karel SOUČEK (203 Czech Republic, belonging to the institution), Lubor BORSIG and Petr BENEŠ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.000

RIV identification code

RIV/00216224:14310/22:00125156

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1007/s10585-021-10145-4

UT WoS

000740192800001

Keywords in English

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

Abstract

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.

Links

NV18-07-00073, research and development project

Name: c-Myb a jeho transkripční program ve fyziologických a patologických osteogenních procesech

Investor: Ministry of Health of the CR

Citovat

ŘÍHOVÁ, Kamila, Monika DÚCKA, Iva STANICZKOVÁ ZAMBO, Ladislava VYMĚTALOVÁ, Martin ŠRÁMEK, Filip TRČKA, Jan VERNER, 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 and Petr BENEŠ. Transcription factor c-Myb: novel prognostic factor in osteosarcoma. Clinical & Experimental Metastasis. Springer, 2022, vol. 39, No 2, p. 375-390. ISSN 0262-0898. Available from: https://dx.doi.org/10.1007/s10585-021-10145-4.

@article{1819457,
   author = {Říhová, Kamila and Dúcka, Monika and Staniczková Zambo, Iva and Vymětalová, Ladislava and Šrámek, Martin and Trčka, Filip and Verner, Jan and Drápela, Stanislav and Fedr, Radek and Suchánková, Tereza and Pavlatovská, Barbora and Ondroušková, Eva and Kubelková, Irena and Zapletalová, Danica and Tuček, Štěpán and Múdry, Peter and Adámková Krákorová, Dagmar and Knopfová, Lucia and Šmarda, Jan and Souček, Karel and Borsig, Lubor and Beneš, Petr},
   article_number = {2},
   doi = {http://dx.doi.org/10.1007/s10585-021-10145-4},
   keywords = {c-Myb; Chemoresistance; Metastasis; Osteosarcoma; Prognosis; Proliferation},
   language = {eng},
   issn = {0262-0898},
   journal = {Clinical & Experimental Metastasis},
   title = {Transcription factor c-Myb: novel prognostic factor in osteosarcoma},
   url = {https://link.springer.com/article/10.1007%2Fs10585-021-10145-4},
   volume = {39},
   year = {2022}
}

TY  - JOUR
ID  - 1819457
AU  - Říhová, Kamila - Dúcka, Monika - Staniczková Zambo, Iva - Vymětalová, Ladislava - Šrámek, Martin - Trčka, Filip - Verner, Jan - Drápela, Stanislav - Fedr, Radek - Suchánková, Tereza - Pavlatovská, Barbora - Ondroušková, Eva - Kubelková, Irena - Zapletalová, Danica - Tuček, Štěpán - Múdry, Peter - Adámková Krákorová, Dagmar - Knopfová, Lucia - Šmarda, Jan - Souček, Karel - Borsig, Lubor - Beneš, Petr
PY  - 2022
TI  - Transcription factor c-Myb: novel prognostic factor in osteosarcoma
JF  - Clinical & Experimental Metastasis
VL  - 39
IS  - 2
SP  - 375-390
EP  - 375-390
PB  - Springer
SN  - 02620898
KW  - c-Myb
KW  - Chemoresistance
KW  - Metastasis
KW  - Osteosarcoma
KW  - Prognosis
KW  - Proliferation
UR  - https://link.springer.com/article/10.1007%2Fs10585-021-10145-4
N2  - 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.
ER  -

ŘÍHOVÁ, Kamila, Monika DÚCKA, Iva STANICZKOVÁ ZAMBO, Ladislava VYMĚTALOVÁ, Martin ŠRÁMEK, Filip TRČKA, Jan VERNER, 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 and Petr BENEŠ. Transcription factor c-Myb: novel prognostic factor in osteosarcoma. \textit{Clinical \&{} Experimental Metastasis}. Springer, 2022, vol.~39, No~2, p.~375-390. ISSN~0262-0898. Available from: https://dx.doi.org/10.1007/s10585-021-10145-4.

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