Wnt and β-Catenin Signaling in the Bone Metastasis of Prostate Cancer

Abstract

Wnt family proteins and β-catenin are critical for the regulation of many developmental and oncogenic processes. Wnts are secreted protein ligands which signal using a canonical pathway, and involve the transcriptional co-activator β-catenin or non-canonical pathways that are independent of β-catenin. Bone metastasis is unfortunately a common occurrence in prostate cancer and can be conceptualized as a series of related steps or processes, most of which are regulated by Wnt ligands and/or β-catenin. At the primary tumor site, cancer cells often take on mesenchymal properties, termed epithelial mesenchymal transition (EMT), which are regulated in part by the Wnt receptor FZD4. Then, Wnt signaling, especially Wnt5A, is of importance as the cells circulate in the blood stream. Upon arriving in the bones, cancer cells migrate and take on stem-like or tumorigenic properties, as aided through Wnt or β-catenin signaling involving CHD11, CD24, and Wnt5A. Additionally, cancer cells can become dormant and evade therapy, in part due to regulation by Wnt5A. In the bones, E-selectin can aid in the reversal of EMT, a process termed mesenchymal epithelial transition (MET), as a part of metastatic tumorigenesis. Once bone tumors are established, Wnt/β-catenin signaling is involved in the suppression of osteoblast function largely through DKK1.

UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer

“…S10 C & D). β-catenin, as a product of the oncogene CTNNB1, has been reported to be involved in WNT signalling and plays a significant role in tumour cell EMT and cancer metastasis 19 . Therefore, we detected the expression of epithelial and mesenchymal proteins as markers of EMT by western blotting.…”

“…Multiple signalling pathways have been identified to involve in EMT, and the role of WNT/β-catenin signalling in EMT is more prominent in a variety of cancers, including PCa 18 . WNT/β-catenin signalling activation facilitates bone metastasis of PCa by promoting tumour cells dissemination, homing and dormancy 19 . Abnormal ubiquitination of β-catenin is one of the mechanisms of WNT signalling activation.…”

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

“…Among the second category, the role of the Wnt5a/NF-κB has been particularly investigated in the context of studies on tumor microenvironment, revealing how an aberrant expression of Wnt5a is immunosuppressive (Lopez-Bergami and Barbero, 2020). In bone metastasis from prostate cancer, the Wnt receptor FZD4 was also reported to play an important role together with Wnt5a (Kaplan et al, 2021). Complementary investigations on this ligand suggest that Wnt5a is integrated into a larger regulatory circuit involving β-catenin, YAP/TAZ, and large tumor suppressor kinase 1/2 (LATS1/2) (Figure 3), with Wnt5a and yes-associated protein 1 (YAP1) both being regulated at the transcriptional level by both Wnt and Hippo pathways (Astudillo 2021).…”

Roles of lncRNAs Mediating Wnt/β-Catenin Signaling in HCC

“…Simultaneously expression of miR-1827 presented increasing after knock of ASB16-AS1, which indicated the fact that activity of miR-1827 might be controlled by lncRNA ASB16-AS1. FZD4 (Frizzled class receptor 4) is regard as the significant molecule to active Wnt/β-catenin signaling pathway ( 128 ). Upregulated miR-1827 could negatively mediated expression of FZD4 to inhibit progression of HCC.…”