Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma

Autor(es)

Nagahashi Marie, Suely Kazue ^{[1, 2]} ; Oba-Shinjo, Sueli Mieko ^[2] ; da Silva, Roseli ^[2] ; Gimenez, Marcela ^{[3, 4]} ; Reis, Gisele Nunes ^[2] ; Tassan, Jean-Pierre ^[5] ; Rosa, Jose Cesar ^{[3, 4]} ; Uno, Miyuki ^{[5, 6]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ctr Studies Cellular & Mol Therapy NETCEM, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Neurol, Lab Mol & Cellular Biol LIM 15, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Prot Chem Ctr, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Mol & Cell Biol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto - Brazil

^[5] Univ Rennes 1, Inst Genet & Dev Rennes, UMR CNRS 6290, Cell Cycle Grp, SFR Biosit, 2 Ave Prof Leon Bernard, CS 3431735043 Rennes, Bretagne - France

^[6] Inst Canc Estado Sao Paulo, Ctr Translat Res Oncol, Av Dr Arnaldo 251, 8th Floor, BR-01246000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROTEOME SCIENCE; v. 14, MAR 11 2016.
• Citações Web of Science: 6

Resumo

Background: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in cell cycle, differentiation, proliferation, and apoptosis. These multiple features are consistent with it being a potential anticancer target. Nevertheless, the MELK pathway in tumorigenesis is not yet completely understood. This study aims to identify proteins associated with MELK pathway in astrocytomas. To this end, proteomic data of the human glioma cell line U87MG transfected with siRNA for MELK were compared with non-target transfected control cells and compared with oligonucleotide microarray data. Results: In both assays, we identified stathmin/oncoprotein 18 (STMN1), involved in cell cycle. STMN1 gene expression was further assessed in a series of 154 astrocytomas and 22 non-neoplastic brain samples by qRT-PCR. STMN1 expression was significantly increased in malignant diffusely infiltrative astrocytomas compared with pilocytic astrocytoma (p < 0.0001). A strong correlation between MELK and STMN1 expressions was observed (r = 0.741, p < 0.0001) in glioblastoma (GBM) samples. However, no difference on survival times was found when compared GBM cases with upregulated and downregulated STMN1 (Breslow = 0.092, median survival time: 11 and 13 months, respectively). Functional assays knocking down MELK by siRNA in GBM cell line showed that gene and protein expression of both MELK and stathmin were diminished. On the other hand, when the same analysis was performed for STMN1, only stathmin gene and protein was silenced. Conclusions: The results presented herein point stahtmin as a downstream target in the MELK pathway that plays a role in malignant progression of astrocytomas. (AU)

• Processo FAPESP: 01/12898-4 - Genoma clínico
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA
• Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/15896-7 - Análise de expressão de genes relacionados a via de MELK em astrocitomas
• Beneficiário: Miyuki Uno
• Modalidade de apoio: Auxílio à Pesquisa - Regular