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.
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.
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.
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.
The measurement of β-catenin expression levels in peripheral blood from patients could be used for early diagnosis of renal carcinoma, which is of great clinical significance.
In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-catenin signaling pathway activation and SNAIL expression.
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.
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.
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.
These findings suggest Wnt signaling pathway activation only in a minority of renal cell carcinomas in young patients.CTNNB1 mutations are rare events.
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.
The present study attempted to clarify the significance of aberrant expression of beta-catenin protein and mutation of exon 3 of the beta-catenin gene in renal and urothelial carcinogenesis. beta-Catenin expression was examined immunohistochemically and mutation of the beta-catenin gene was analyzed by polymerase chain reaction-single strand conformation polymorphism (SSCP) and direct sequencing. beta-Catenin immunoreactivity was observed at the cell membrane in all 30 renal cell carcinomas (RCC) examined, and no RCC showed a mobility-shifted SSCP band.
In conclusion, this study demonstrates that beta-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of beta-catenin protein are found only in conventional (clear cell) renal carcinomas.