Upregulation of p38 pathway accelerates proliferation and migration of MDA-MB-231 breast cancer cells

Huth,Hugo  W.; Santos,Daniel  M.; Gravina,Humberto  D.; Resende,Jarbas  M.; Goes,Alfredo  M.; de Lima,Maria   Elena; Ropert,Catherine

doi:10.3892/or.2017.5452

Upregulation of p38 pathway accelerates proliferation and migration of MDA-MB-231 breast cancer cells

Authors:
- Hugo W. Huth
- Daniel M. Santos
- Humberto D. Gravina
- Jarbas M. Resende
- Alfredo M. Goes
- Maria Elena de Lima
- Catherine Ropert
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Affiliations: Department of Physiology and Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270-910, Brazil, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270-910, Brazil, Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270-910, Brazil
Published online on: February 14, 2017 https://doi.org/10.3892/or.2017.5452
Pages: 2497-2505

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Abstract

Tumor cells capture the signaling pathways used by normal tissue to promote their own survival and dissemination and among them, the NF-κB and MAPK pathways (ERK, JNK and p38). MAPK activation has ambiguous effects on tumor cell fate depending on cell type, cancer stage and the engaged MAPK isoforms. A synthetic peptide named LyeTx II, derived from the venom of the Brazilian spider Lycosa erythrognatha, was capable of increasing MDA-MB-231 aggressive breast cancer cell proliferation as indicated by MTT and BrdU (5-bromo-2'-deoxyuridine) incorporation assay and cell migration. A correlation has been established between the accelerated proliferation and migration observed in the presence of LyeTx II and the upregulation of p38 MAPK phosphorylation. The use of the selective inhibitor of p38α/β (SB203580) abrogated the peptide effect in MDA-MB-231 cells. Besides, an augment of the canonical NF-κB pathway activation considered as crucial in cancer progression was noted after cell incubation with LyeTx II. Importantly, activation of p38 and NF-κB pathways was dependent on TAK1 activity. Together, these data suggest that TAK1-p38 pathway may represent an interesting target for treatment of aggressive breast cancers.

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