Metalloprotease ADAMTS-1 decreases cell migration and invasion modulating the spatiotemporal dynamics of Cdc42 activity

Autor(es)

Lima, Maira de Assis ^[1] ; da Silva, Suely Vieira ^[1] ; Serrano-Garrido, Orlando ^[2] ; Huelsemann, Maren ^{[3, 4]} ; Santos-Neres, Luana ^[1] ; Carlos Rodriguez-Manzaneque, Juan ^[2] ; Hodgson, Louis ^{[3, 4]} ; Freitas, Vanessa M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes 1524, Ed Biomed 1 Sala 428, BR-05508000 Sao Paulo, SP - Brazil

^[2] GENYO, Ctr Genom & Oncol Res, Ave Ilustrac 114, Granada 18016 - Spain

^[3] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 - USA

^[4] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10461 - USA

• Tipo de documento: Artigo Científico
• Fonte: CELLULAR SIGNALLING; v. 77, JAN 2021.
• Citações Web of Science: 1

Resumo

ADAMTSs (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) are secreted proteases dependent on Zn2+/Ca2+, involved in physiological and pathological processes and are part of the extracellular matrix (ECM). Here, we investigated if ADAMTS-1 is required for invasion and migration of cells and the possible mechanism involved. In order to test ADAMTS-1's role in ovarian cancer cells (CHO, NIH-OVCAR-3 and ES2) and NIH-3 T3 fibroblasts, we modified the levels of ADAMTS-1 and compared those to parental. Cells exposed to ADAMTS-1-enriched medium exhibited a decline in cell migration and invasion when compared to controls with or without a functional metalloproteinase domain. The opposite was observed in cells when ADAMTS-1 was deleted via the CRISPR/Cas9 approach. The decline in ADAMTS-1 levels enhanced the phosphorylated form of Src and FAX. We also evaluated the activities of cellular Rho GTPases from cell lysates using the GLISA (R) kit. The Cdc42-GTP signal was significantly increased in the CRISPR ADAMTS-1 ES-2 cells. By a Fodrster resonance energy transfer (FRET) biosensor for Cdc42 activity in ES-2 cells we demonstrated that Cdc42 activity was strongly polarized at the leading edge of migrating cells with ADAMTS-1 deletion, compared to the wild type cells. As conclusion, ADAMTS-1 inhibits proliferation, polarization and migration. (AU)

• Processo FAPESP: 15/19773-5 - Função da progesterona e da protease ADAMTS 1 na migração de células derivadas de câncer de ovário
• Beneficiário: Maíra de Assis Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/19813-5 - Função da progesterona e da protease ADAMTS 1 na migração de células derivadas de câncer de ovário
• Beneficiário: Maíra de Assis Lima
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 18/05566-6 - ADAMTS-1 nuclear regulando o comportamento de células normais e neoplásicas
• Beneficiário: Vanessa Morais Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Regular