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EcTI impairs survival and proliferation pathways in triple-negative breast cancer by modulating cell-glycosaminoglycans and inflammatory cytokines.

Authors
  • Lobo, Yara A1
  • Bonazza, Camila2
  • Batista, Fabrício P1
  • Castro, Rodrigo A2
  • Bonturi, Camila R1
  • Salu, Bruno R1
  • de Cassia Sinigaglia, Rita3
  • Toma, Leny1
  • Vicente, Carolina M1
  • Pidde, Giselle4
  • Tambourgi, Denise V4
  • Alvarez-Flores, Miryam P5
  • Chudzinski-Tavassi, Ana M5
  • Oliva, Maria Luiza V6
  • 1 Biochemistry, Universidade Federal de São Paulo, 04044-020, São Paulo, SP, Brazil. , (Brazil)
  • 2 Gynecology, Universidade Federal de São Paulo, 04044-020, São Paulo, SP, Brazil. , (Brazil)
  • 3 Electron Microscopy Center at the Universidade Federal de São Paulo, 04044-020, São Paulo, SP, Brazil. , (Brazil)
  • 4 Immunochemistry, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, Brazil. , (Brazil)
  • 5 Center of Excellence in New Target Discovery (CENTD), Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, Brazil. , (Brazil)
  • 6 Biochemistry, Universidade Federal de São Paulo, 04044-020, São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
Cancer letters
Publication Date
Aug 22, 2020
Volume
491
Pages
108–120
Identifiers
DOI: 10.1016/j.canlet.2020.08.017
PMID: 32841713
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Breast cancer is the most common malignant tumor among women worldwide, and triple-negative breast cancer is the most aggressive type of breast cancer, which does not respond to hormonal therapies. The protease inhibitor, EcTI, extracted from seeds of Enterolobium contortisiliquum, acts on the main signaling pathways of the MDA-MB-231 triple-negative breast cancer cells. This inhibitor, when bound to collagen I of the extracellular matrix, triggers a series of pathways capable of decreasing the viability, adhesion, migration, and invasion of these cells. This inhibitor can interfere in the cell cycle process through the main signaling pathways such as the adhesion, Integrin/FAK/SRC, Akt, ERK, and the cell death pathway BAX and BCL-2. It also acts by reducing the main inflammatory cytokines such as TGF-α, IL-6, IL-8, and MCP-1, besides NFκB, a transcription factor, responsible for the aggressive and metastatic characteristics of this type of tumor. Thus, the inhibitor was able to reduce the main processes of carcinogenesis of this type of cancer. Copyright © 2020 Elsevier B.V. All rights reserved.

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