FUND: This study was supported by the University of Luxembourg (IRP grant scheme; R-AGR-0755-12), the Luxembourg National Research Fund (FNR PRIDE PRIDE15/10675146/CANBIO), the Fondation Cancer (Luxembourg), the European Union's Horizon2020 research and innovation programme under the Marie Sklodowska- Curie grant agreement No 642295 (MEL-PLEX), and the German Federal Ministry of Education and Research (BMBF) within the project MelanomSensitivity (BMBF/BM/7643621).
Gibbs sampling identified two disturbed pathways (pathways in cancer and influenza A) and two hub genes (cyclin A1 and WNT2) under the adjusted probability >0.8.
In this study, we suggest a possible interaction mode of Wnt2 with the Fzd7 cysteine-rich domain (CRD)-both of which are up-regulated in some types of cancer.
Three-dimensional organotypic co-culture assays revealed that WNT2-mediated fibroblast motility and extracellular matrix remodeling enhanced cancer cell invasion of cell lines even harboring mutations in the adenomatous polyposis coli/β-catenin pathway.
Collectively, these data demonstrate an apparent pro-oncogenic activity of IRP2 that depends on its specific 73 amino acids insert, and provide further evidence for a link between IRPs and cancer biology.
Our results show that the overexpression of IRP1 is associated with an apparent tumor suppressor phenotype and provide a direct regulatory link between the IRE/IRP system and cancer.
Wnt-2 was up-regulated in all of the cancer lesions and 13.0% (3/23) of the normal breast tissues, whereas Wnt-1 was expressed in both the cancer and normal breast tissues of the five cases examined.
Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion.