| Full text | |
| Author(s): |
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]
Total Authors: 8
|
| Affiliation: | [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
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | CELLULAR SIGNALLING; v. 77, JAN 2021. |
| Web of Science Citations: | 1 |
| Abstract | |
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) | |
| FAPESP's process: | 15/19773-5 - Functions of progesterone and ADAMTS 1 protease in the migration of cells derived from ovarian cancer |
| Grantee: | Maíra de Assis Lima |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/19813-5 - Function of progesterone and ADAMTS 1 in the migration of cells derived from ovarian cancer |
| Grantee: | Maíra de Assis Lima |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 18/05566-6 - Nuclear ADAMTS-1 regulating normal and cancer cells |
| Grantee: | Vanessa Morais Freitas |
| Support Opportunities: | Regular Research Grants |