Mechanistically, calcitriol suppressed EMT through different signaling pathways: (1) calcitriol suppressed Smad2/3 phosphorylation through reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-β1-stimulated RCC cells; (2) calcitriol inhibited STAT3 activation in LPS-stimulated RCC cells; (3) calcitriol inhibited β-catenin/TCF-4 activation through promoting integration of VDR with β-catenin in TGF-β1-unstimulated RCC cells.
In a large series of RCC with TT of VC high IHC expression of E-cadherin and β-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS.
miR-200c-3p, SOX2, β-catenin and GSK3β expression in both tissues and cells of RCC were detected by RT-qPCR or western blot analysis. miR-200c-3p was restored or silenced to determine their biological functions of RCC cells.
Higher levels of Wnt3a and β-catenin were also found in xenografts of QKI-knockdown clear cell renal cell carcinoma (ccRCC) CAKI-1 cells by western blot analysis and immumohistochemical staining.
Numerous signaling pathways, such as PI3K/Akt/mTOR and Wnt‑β‑catenin have been demonstrated to be associated with the tumorigenesis and development of RCC.
Cytoplasmic β-catenin expression is an independent prognostic factor for conventional RCC, and may help to identify patients with a high risk of cancer-specific death and to direct optimized active surveillance or adjuvant therapy.
The effects in the combination group were driven by the Akt/GSK-3β/β-catenin signaling pathway, and deregulation of β-catenin expression was predictive of poor outcome in ccRCC patients.
These results highlight a new role for Ror2 in conveying a tonic signal to stabilize soluble β-catenin and create a poised state of enhanced responsiveness to Wnt3a exogenous signals in RCC.
Ptprz1-enhanced RCC cells' proliferation depends on VHL inactivation, and the Ptprz1/β-catenin pathway may be a potential target for treating RCC with inactive VHL.
Molecular validation of cell line models with gain- or loss-of-function designs showed that forced WNT10A expression induced RCC cell proliferation and aggressiveness, including higher chemoresistance, cell migration, invasiveness, and cell transformation, due to the activation of β-catenin-dependent signaling.
Beyond well-validated signaling targets such as VHL, VEGFR and mTOR, additional pathways including HGF/c-MET and Wnt/β-catenin have emerged as important to RCC pathogenesis.
Increased cell invasiveness is mediated by another ubiquitin ligase target with relevance to the molecular pathogenesis of renal cell carcinoma: beta-catenin.
However, previous immunohistochemical studies on beta-catenin have suggested that activation of the canonical Wnt pathway through beta-catenin stabilization is infrequent in RCC.
To test this hypothesis, we investigated TCF-4 splicing isoforms, beta-catenin, and Wnt signal pathway (cyclin D1, c-myc, c-jun, and MMP7) in three RCC cell lines (A498, Caki-1, and Caki-2), 38 primary RCCs, and 29 normal kidney samples.
However, the cytoplasmic accumulations of beta-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas.