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.
2011
Procházková, Jirina; Kabátková, Markéta; Bryja, Vítezslav; Umannová, Lenka; Bernatík, Ondrej; Kozubík, Alois; Machala, Miroslav; Vondrácek, Jan
In: Toxicological sciences : an official journal of the Society of Toxicology, vol. 122, no. 2, pp. 349–360, 2011, ISSN: 1096-0929, (Place: United States).
Abstract | Links | BibTeX | Tags: Animals, Aryl Hydrocarbon Hydroxylases/genetics/metabolism, Aryl Hydrocarbon/genetics/*metabolism, beta Catenin/genetics/*metabolism, Cadherins/genetics, Cell Adhesion, Cell Differentiation, Cell Line, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P-450 CYP1B1, Down-Regulation/drug effects, Hepatocytes/drug effects, Inbred F344, Liver/*drug effects, Polychlorinated Dibenzodioxins/toxicity, Rats, Receptors, Wnt Proteins/genetics/*metabolism, Wnt Signaling Pathway
@article{prochazkova_interplay_2011,
title = {The interplay of the aryl hydrocarbon receptor and β-catenin alters both AhR-dependent transcription and Wnt/β-catenin signaling in liver progenitors.},
author = {Jirina Procházková and Markéta Kabátková and Vítezslav Bryja and Lenka Umannová and Ondrej Bernatík and Alois Kozubík and Miroslav Machala and Jan Vondrácek},
doi = {10.1093/toxsci/kfr129},
issn = {1096-0929},
year = {2011},
date = {2011-08-01},
journal = {Toxicological sciences : an official journal of the Society of Toxicology},
volume = {122},
number = {2},
pages = {349–360},
abstract = {β-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/β-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/β-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/β-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active β-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/β-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors. The downregulation of β-catenin was also related to a reduced cell adhesion, disruption of E-cadherin-mediated cell-cell junctions and an increased G1-S transition in liver progenitor cell line. In conclusion, although β-catenin augmented the expression of selected AhR target genes, the persistent AhR activation may lead to downregulation of Wnt/β-catenin signaling, thus altering differentiation and/or proliferative status of liver progenitor cells.},
note = {Place: United States},
keywords = {Animals, Aryl Hydrocarbon Hydroxylases/genetics/metabolism, Aryl Hydrocarbon/genetics/*metabolism, beta Catenin/genetics/*metabolism, Cadherins/genetics, Cell Adhesion, Cell Differentiation, Cell Line, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P-450 CYP1B1, Down-Regulation/drug effects, Hepatocytes/drug effects, Inbred F344, Liver/*drug effects, Polychlorinated Dibenzodioxins/toxicity, Rats, Receptors, Wnt Proteins/genetics/*metabolism, Wnt Signaling Pathway},
pubstate = {published},
tppubtype = {article}
}
β-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/β-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/β-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/β-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active β-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/β-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors. The downregulation of β-catenin was also related to a reduced cell adhesion, disruption of E-cadherin-mediated cell-cell junctions and an increased G1-S transition in liver progenitor cell line. In conclusion, although β-catenin augmented the expression of selected AhR target genes, the persistent AhR activation may lead to downregulation of Wnt/β-catenin signaling, thus altering differentiation and/or proliferative status of liver progenitor cells.