Wnt/β-catenin signaling contributes to prostate cancer heterogeneity through reciprocal suppression of H3K27 trimethylation

Glucocorticoid Receptor and β-Catenin Interact in Prostate Cancer Cells and Their Co-Inhibition Attenuates Tumorsphere Formation, Stemness, and Docetaxel Resistance

“…Although the contribution of Wnt/β-catenin to PCa stemness is well established [ 33 , 46 , 79 ], knowledge of mechanisms underlying its role in chemoresistance is still limited. Recently, PC3 and DU145 cells with active Wnt/β-catenin signaling exhibited CSC properties, higher resistance to DTX, and suppression of H3K27 trimethylation, contributing to PCa heterogeneity [ 80 ]. Wnt/β-catenin signaling was also reported to be activated by the E3 ubiquitin ligase EDD in DU145 and 22rv1 cells, leading to increased DTX resistance [ 36 ].…”

Trifuhalol A, a phlorotannin from the brown algae Agarum cribrosum, reduces adipogenesis of human primary adipocytes through Wnt/β-catenin and AMPK-dependent pathways

“…When the canonical Wnt pathway is not activated, the destruction complex (composed of glycogen synthase kinase 3 beta, GSK3β, axin, adenomatous polyposis coli, casein kinase-1, and β-transducin) remains active, and GSK3β phosphorylates β-catenin leading to degradation of β-catenin ( Pakula et al, 2017 ). The canonical Wnt pathway is activated when frizzled 1 or its co-receptor lipoprotein receptor-related protein (LRP) 5/6 binds with one of the canonical Wnt ligands (such as Wnt family member 1, 3a, and 10b; Wnt1, Wnt3a, Wnt10b), leading to inhibition of the destruction complex; thus, β-catenin enters the nucleus to start transcription of downstream genes ( Wang et al, 2020 ). In this study, we examined the effects of trifuhalol A in canonical Wnt/β-catenin signaling pathway: Wnt family member 10b (Wnt10b), frizzled 1, LRP 6 and GSK-3β.…”

“…Phosphorylated LKB1 protein induces phosphorylated AMPK, which inhibits lipogenesis. In addition, the AMPK pathway is reported to interplay with the canonical Wnt/β-catenin pathway ( Zhao et al, 2010 ), and GSK-3β is inhibited by the AMPK pathway ( Wang et al, 2020 ). Our results showed that trifuhalol A increased the levels of p AMPK and p LKB1 ( Fig.…”

KDM6 Demethylases and Their Roles in Human Cancers

“…Nevertheless, KDM6A cannot be perceived solely as a tumor suppressor, as KDM6A is found to have close association with genesis and progression of different cancers ( 25 , 74 , 77 , 78 , 80 ). In advanced stages of prostate cancer, KDM6A is essential for maintenance of androgen receptor (AR) activity despite anti-androgenic therapy ( 77 , 78 , 124 ). A different pro-oncogenic function has been shown in cervical cancer, where increased KDM6A expression appears to support cell cycle activation by p21CIP1 suppression of replication stress ( 80 ).…”