The lipid raft protein NTAL participates in AKT signaling in mantle cell lymphoma

Autor(es):Mostrar menos -

Ferreira, Germano Aguiar ^{[1, 2]} ; Thome, Carolina Hassibe ^{[1, 2]} ; Sper Simao, Ana Maria ^[3] ; Scheucher, Priscila Santos ^{[4, 2]} ; Araujo Silva, Cleide Lucia ^[2] ; Chahud, Fernando ^[5] ; Ciancaglini, Pietro ^[3] ; Leopoldino, Andreia Machado ^{[2, 6]} ; Rego, Eduardo Magalhaes ^{[4, 2]} ; Faca, Vitor Marcel ^{[1, 2]} ; dos Santos, Guilherme Augusto ^{[2, 7]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[2] Hemoctr Ribeirao Preto, BR-14051140 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Chem, Fac Philosophy Sci & Letters Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Dept Pathol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Dept Clin Toxicol & Bromatol Analyzes, Fac Pharmaceut Sci Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[7] Univ Ribeirao Preto UNAERP, Dept Med, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Leukemia & Lymphoma; v. 60, n. 11 MAY 2019.
• Citações Web of Science: 0

Resumo

Lipid rafts are ordered membrane domains, which provide an environment for the proteins participating in signal transduction. Perifosine is an alkylphospholipid (APL) that inhibits the AKT pathway, cytotoxic to neoplastic cells. We have shown that the lipid raft adaptor protein NTAL is a target of APLs in leukemic cells. Using human mantle cell lymphoma (MCL) Granta-519 cell line we showed here that perifosine decreased NTAL in lipid raft fractions reducing AKT phosphorylation before apoptosis. We also showed that the NTAL-knockdown by shRNA induced a state of reduced AKT activation. Experimental NTAL-knockdown in NSG mouse MCL xenografts reduced AKT activity, increased the basal apoptotic rate by 3-fold (n = 8) and decreased tumor weight by 2.7-fold (n = 5), indicating that NTAL participates in tumor growth. NTAL protein was detected by western blotting in circulating cells of 7 of 8 MCL patients in the leukemic phase, suggesting involvement in the progression of the disease. (AU)

• Processo FAPESP: 13/07675-3 - Estudo da via de sinalização pi3k/akt em leucemia mielóide aguda utilizando o monitoramento seletivo de ions (srm).
• Beneficiário: Carolina Hassibe Thomé
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado