2022
Říhová, Kamila; Dúcka, Monika; Zambo, Iva Staniczková; 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; Krákorová, Dagmar Adámková; Knopfová, Lucia; Šmarda, Jan; Souček, Karel; Borsig, Lubor; Beneš, Petr
Transcription factor c-Myb: novel prognostic factor in osteosarcoma. Journal Article
In: Clinical & experimental metastasis, vol. 39, no. 2, pp. 375–390, 2022, ISSN: 1573-7276 0262-0898, (Place: Netherlands).
Abstract | Links | BibTeX | Tags: *Bone Neoplasms/pathology, *Osteosarcoma/pathology, Animals, c-Myb, Cell Line, Cell Movement/genetics, Cell Proliferation, Chemoresistance, Gene Expression Regulation, Humans, Metastasis, Mice, Neoplastic, Osteosarcoma, Prognosis, proliferation, Retrospective Studies, Tumor, Wnt Signaling Pathway
@article{rihova_transcription_2022,
title = {Transcription factor c-Myb: novel prognostic factor in osteosarcoma.},
author = {Kamila Říhová and Monika Dúcka and Iva Staniczková Zambo and Ladislava Vymětalová and Martin Šrámek and Filip Trčka and Jan Verner and Stanislav Drápela and Radek Fedr and Tereza Suchánková and Barbora Pavlatovská and Eva Ondroušková and Irena Kubelková and Danica Zapletalová and Štěpán Tuček and Peter Múdry and Dagmar Adámková Krákorová and Lucia Knopfová and Jan Šmarda and Karel Souček and Lubor Borsig and Petr Beneš},
doi = {10.1007/s10585-021-10145-4},
issn = {1573-7276 0262-0898},
year = {2022},
date = {2022-04-01},
journal = {Clinical & experimental metastasis},
volume = {39},
number = {2},
pages = {375–390},
abstract = {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.},
note = {Place: Netherlands},
keywords = {*Bone Neoplasms/pathology, *Osteosarcoma/pathology, Animals, c-Myb, Cell Line, Cell Movement/genetics, Cell Proliferation, Chemoresistance, Gene Expression Regulation, Humans, Metastasis, Mice, Neoplastic, Osteosarcoma, Prognosis, proliferation, Retrospective Studies, Tumor, Wnt Signaling Pathway},
pubstate = {published},
tppubtype = {article}
}
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.