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Transcription factor c-Myb: novel prognostic factor in osteosarcoma
- 1.0556525 - BFÚ 2023 RIV NL eng J - Journal Article
Říhová, K. - Ducka, M. - Zambo, I. - Vymětalová, L. - Šrámek, M. - Trčka, F. - Verner, J. - Drápela, Stanislav - Fedr, Radek - Suchánková, Tereza - Pavlatovska, B. - Ondroušková, E. - Kubelkova, I. - Zapletalová, D. - Tucek, S. - Mudry, P. - Krakorova, D. - Knopfová, L. - Šmarda, J. - Souček, Karel - Borsig, L. - Beneš, P.
Transcription factor c-Myb: novel prognostic factor in osteosarcoma.
Clinical & Experimental Metastasis. Roč. 39, č. 2 (2022), s. 375-390. ISSN 0262-0898. E-ISSN 1573-7276
R&D Projects: GA ČR(CZ) GA20-22984S
Institutional support: RVO:68081707
Keywords : acute myeloid-leukemia * colorectal-cancer * down-regulation * expression * metastasis * stress
OECD category: Oncology
Impact factor: 4, year: 2022
Method of publishing: Limited access
https://link.springer.com/article/10.1007/s10585-021-10145-4
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.
Permanent Link: https://hdl.handle.net/11104/0340442
Number of the records: 1