SPARC induces E-cadherin repression and enhances cell migration through integrin v beta 3 and the transcription factor ZEB1 in prostate cancer cells
Author
dc.contributor.author
López Moncada, Fernanda
Author
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Torres Torres, María José
Author
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Lavanderos Andrade, Boris
Author
dc.contributor.author
Cerda Arancibia, Oscar
Author
dc.contributor.author
Castellón Vera, Enrique
Author
dc.contributor.author
Contreras Muñoz, Héctor
Admission date
dc.date.accessioned
2022-07-21T13:56:47Z
Available date
dc.date.available
2022-07-21T13:56:47Z
Publication date
dc.date.issued
2022
Cita de ítem
dc.identifier.citation
Int. J. Mol. Sci. 2022, 23, 5874.
es_ES
Identifier
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10.3390/ijms23115874
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/186858
Abstract
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Secreted protein acidic and rich in cysteine (SPARC), or osteonectin, is a matricellular protein that modulates interactions between cells and their microenvironment. SPARC is expressed during extracellular matrix remodeling and is abundant in bone marrow and high-grade prostate cancer (PCa). In PCa, SPARC induces changes associated with epithelial-mesenchymal transition (EMT), enhancing migration and invasion and increasing the expression of EMT transcriptional factor Zinc finger E-box-binding homeobox 1 (ZEB1), but not Zinc finger protein SNAI1 (Snail) or Zinc finger protein SNAI2 (Slug). It is unknown whether the SPARC-induced downregulation of E-cadherin in PCa cells depends on ZEB1. Several integrins are mediators of SPARC effects in cancer cells. Because integrin signaling can induce EMT programs, we hypothesize that SPARC induces E-cadherin repression through the activation of integrins and ZEB1. Through stable knockdown and the overexpression of SPARC in PCa cells, we demonstrate that SPARC downregulates E-cadherin and increases vimentin, ZEB1, and integrin beta 3 expression. Knocking down SPARC in PCa cells decreases the tyrosine-925 phosphorylation of FAK and impairs focal adhesion formation. Blocking integrin alpha v beta 3 and silencing ZEB1 revert both the SPARC-induced downregulation of E-cadherin and cell migration enhancement. We conclude that SPARC induces E-cadherin repression and enhances PCa cell migration through the integrin alpha v beta 3/ZEB1 signaling pathway.
es_ES
Patrocinador
dc.description.sponsorship
National Fund for Science and Technology (FONDECYT) of the National Agency for Investigation and Development (ANID) FONDECYT 1151214
FONDECYT 1200917
FONDECYT 1201704
Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD) fund
Iniciativa Cientifica Milenio of the National Agency of Research and Development (ANID) , URedes
University of Chile URC424 Nffi 007/17
National Agency for Investigation and Development (ANID) 21160886
21160703
es_ES
Lenguage
dc.language.iso
en
es_ES
Publisher
dc.publisher
MDPI
es_ES
Type of license
dc.rights
Attribution-NonCommercial-NoDerivs 3.0 United States