Journal
BIOMEDICINES
Volume 9, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines9050515
Keywords
breast cancer; HOXB7; cell phenotype; MDA-MB-231
Categories
Funding
- FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation [POCI-01-0145-FEDER-030562]
- Portuguese funds through FCT-Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior [PTDC/BTM-TEC/30562/2017]
- Portugal 2020
- Fundação para a Ciência e a Tecnologia [PTDC/BTM-TEC/30562/2017] Funding Source: FCT
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HOX genes play a role in breast cancer progression depending on molecular subtypes, with HOXB7 overexpression potentially promoting less aggressive phenotypes in Triple-Negative breast cancer cells.
HOX genes appear to play a role in breast cancer progression in a molecular subtype-dependent way. The altered expression of HOXB7, for example, was reported to promote breast cancer progression in specific subtypes. Here we induced HOXB7 overexpression in MDA-MB-231 cells, a cellular model of the Triple-Negative breast cancer molecular subtype, and evaluated the phenotypic changes in cell viability, morphogenesis, migration, invasion, and colony formation. During the phenotypic characterization of the HOXB7-overexpressing cells, we consistently found less aggressive behavior represented by lower cell viability, inhibition of cell migration, invasion, and attachment-independent colony formation capacities added to the more compact and organized spheroid growth in 3D cultures. We then evaluated the expression of putative downstream targets and their direct binding to HOXB7 comparing ChIP-qPCR data generated from HOXB7-overexpressing cells and controls. In the manipulated cells, we found enriched biding of HOXB7 to CTNNB1, EGFR, FGF2, CDH1, DNMT3B, TGFB2, and COMMD7. Taken together, these results highlight the plasticity of the HOXB7 function in breast cancer, according to the cellular genetic background and expression levels, and provide evidence that in Triple-Negative breast cancer cells, HOXB7 overexpression has the potential to promote less aggressive phenotypes.
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