Wnt/β-catenin signaling: new (and old) players and new insights

Huang, He; He, Xi

doi:10.1016/j.ceb.2008.01.009

Cited by 401 publications

(313 citation statements)

References 50 publications

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“…Follow by, b-catenin translocates to the nucleus, where it binds to TCF/LEF, thereby transcription the expression of various Wnt target genes, for instance, c-Myc and cycinD1, which are related with cell growth. [12][13][14][15] Our groups identified that reexpression of hepaCAM could decrease b-catenin expression. 16 Thereby, we hypothesize that overexpression of hepaCAM may suppress proliferation through Wnt/b-catenin pathway in human bladder cancer cells.…”

Section: Introductionmentioning

confidence: 97%

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

et al. 2015

Cancer Biology & Therapy

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Keywords: bladder cancer, HepaCAM, T24, Wnt/b-catenin Abbreviations: Ad, adenvirus; HepaCAM, hepatocyte cell adhesion molecule.We previously established that hepatocyte cell adhesion molecule (hepaCAM), a typical structure of immunoglobulin (Ig)-like adhesion molecules, inhibited the proliferation and the progression of cultured human bladder cancer cells. As increasing evidence reveals that aberrant activation of canonical Wnt pathway is involved in the pathogenesis of bladder cancer, and b-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the antiproliferation effect of hepaCAM was associated with Wnt/b-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and b-catenin in transitional cell carcinoma of bladder (TCCB) was found. Follow by, studied the effect of hepaCAM on the key elements of Wnt pathway. Here, Our researches showed that hepaCAM played a central role in modulating the Wnt/b-catenin signaling pathway by interfering nuclear protein levels of b-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3b led to elevate the phosphorylation of b-catenin, contributing to the aberrant translocation of b-catenin. In addition, Anti-proliferation and associated molecular mechanisms of hepaCAM were demonstrated by using vivo experiment. In conclusion, our reports uncover that expression of hepaCAM suppresses the proliferation of bladder cancer cells through a Wnt/b-catenin-dependent signaling pathway in vitro and in vivo.

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Section: Introductionmentioning

confidence: 97%

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

et al. 2015

Cancer Biology & Therapy

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“…(1) Wnt/b-catenin pathway activation expands osteoprogenitor cells while reducing osteoblast apoptosis, resulting in bone anabolism. (2) Sclerostin regulates Wnt/b-catenin and influences bone mass.…”

Section: Introductionmentioning

confidence: 99%

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

Ardawi

Rouzi

Al-Sibiani

et al. 2012

Journal of Bone and Mineral Research

126

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Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 AE 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women. ß

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“…b-catenin's oncogenic potential is well documented, and mutations resulting in its stabilization and nuclear accumulation have been observed in various carcinomas (Gavert and Ben-Ze'ev, 2007;Huang and He, 2008;Huber and Weiske, 2008;Jeanes et al, 2008;Jin et al, 2008). In contrast, plakoglobin has typically been associated with tumor/metastasis-suppressor activity, although the mechanism behind this activity is not understood (Simcha et al, 1996;Pantel et al, 1998;Parker et al, 1998;Winn et al, 2002;Reiger-Christ et al, 2005;Kanazawa et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

et al. 2010

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Plakoglobin (c-catenin) is a homolog of b-catenin with similar dual adhesive and signaling functions. The adhesive function of these proteins is mediated by their interactions with cadherins, whereas their signaling activity is regulated by association with various intracellular partners. In this respect, b-catenin has a well-defined oncogenic activity through its role in the Wnt signaling pathway, whereas plakoglobin acts as a tumor/metastasis suppressor through mechanisms that remain unclear. We previously expressed plakoglobin in SCC9 squamous carcinoma cells (SCC9-P) and observed a mesenchymalto-epidermoid transition. Comparison of the protein and RNA profiles of parental SCC9 cells and SCC9-P transfectants identified various differentially expressed proteins and transcripts, including the nonmetastatic protein 23 (Nm23). In this study, we show that Nm23-H1 mRNA and Nm23-H2 protein are increased after plakoglobin expression. Coimmunoprecipitation and confocal microscopy studies using SCC9-P and various epithelial cell lines with endogenous plakoglobin expression revealed that Nm23 interacts with plakoglobin, cadherins and a-catenin. Furthermore, Nm23-H2 is the primary isoform involved in these interactions, which occur prominently in the cytoskeleton-associated pool of cellular proteins. In addition, we show that plakoglobinNm23 interaction requires the N-terminal (a-catenin interacting) domain of plakoglobin. Our data suggest that by increasing the expression and stability of Nm23, plakoglobin has a role in regulating the metastasis suppressor activity of Nm23, which may further provide a potential mechanism for the tumor/metastasis suppressor function of plakoglobin itself.

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Wnt/β-catenin signaling: new (and old) players and new insights

Cited by 401 publications

References 50 publications

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

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