Matrix Rigidity Activates Wnt Signaling through Down-regulation of Dickkopf-1 Protein

Abstract

Background: Metastasizing ovarian cancer (EOC) cells anchor in the submesothelial collagen matrix. Results: Modeling EOC metastasis with cells in three-dimensional collagen culture down-regulates an inhibitor of Wnt signaling, Dickkopf-1. Conclusion: Cell matrix adhesion can activate Wnt signaling in the absence of Wnt pathway mutations. Significance: Cross-talk between adhesion-regulated signaling pathways may fine tune tissue invasive activity.

Lysophosphatidic Acid Initiates Epithelial to Mesenchymal Transition and Induces β-Catenin-mediated Transcription in Epithelial Ovarian Carcinoma

“…This is consistent with data in the current report showing co-localization of E-cadherin at sites of clustered ␤1 integrins. Furthermore, three-dimensional collagen culture induces ␤1 integrin aggregation and down-regulates the expression of dickkopf-1, an inhibitor of canonical Wnt signaling (61,62). These data support a mechanism whereby LPA-induced ␤1 integrin aggregation activates ␤-catenin signaling.…”

Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

“…The MCF-7/MET-R cells notably lost (12-fold downregulation vs. metformin-naïve MCF-7 cells) the expression of the Dickkopf1 (DKK1) gene (Table 2), which encodes a secreted inhibitor of the Wnt/β-catenin pathway and may have tumor suppressor functions. [96][97][98] Exogenous expression of DKK1 in human malignant breast cancer cells with mesenchymallike phenotype significantly reduces the expression of EMTpromoting factors, such as SLUG and TWIST; 99 conversely, silencing DKK1 expression in non-tumorigenic epithelial breast cells leads to increased invasive capacity and decreased E-cadherin expression. 100 Together, these findings strongly suggest that the negative effect of DKK1 on the EMT is part of the suppressive reprogramming that occurs when epithelial MCF-7 breast cancer cells adapt to the continuous presence of metformin.…”

Beyond TGFβ – Novel ways to target airway and parenchymal fibrosis

“…For instance, mechanical stretch, which is partly defined by the composition and extent of the ECM, can lower the expression of the WNT antagonist-DKK1 in a dose-dependent manner, thereby activating WNT/b-catenin signalling [88]. Although the phenomenon is not confirmed in the lungs, decreased abundance of DKK1 in fibrotic lungs could be explained by progressive stiffening of the disease afflicted organ.…”