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SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 May 24; Vol. 23 (11). Date of Electronic Publication: 2022 May 24. - Publication Year :
- 2022
-
Abstract
- 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 β3 expression. Knocking down SPARC in PCa cells decreases the tyrosine-925 phosphorylation of FAK and impairs focal adhesion formation. Blocking integrin αvβ3 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 αvβ3/ZEB1 signaling pathway.
- Subjects :
- Cadherins genetics
Cadherins metabolism
Cell Line, Tumor
Cell Movement genetics
Epithelial-Mesenchymal Transition genetics
Humans
Integrin alphaVbeta3 metabolism
Male
Neoplasm Invasiveness
Osteonectin genetics
Tumor Microenvironment
Zinc Finger E-box-Binding Homeobox 1 genetics
Zinc Finger E-box-Binding Homeobox 1 metabolism
Prostatic Neoplasms genetics
Prostatic Neoplasms metabolism
Transcription Factors genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35682554
- Full Text :
- https://doi.org/10.3390/ijms23115874