Wnt-11 signaling leads to down-regulation of the Wnt/β-catenin, JNK/AP-1 and NF-κB pathways and promotes viability in the CHO-K1 cells

Railo, Antti; Nagy, Irina I.; Kilpeläinen, Pekka; Vainio, Seppo

doi:10.1016/j.yexcr.2008.04.010

Cited by 35 publications

(29 citation statements)

References 66 publications

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“…Our previous data demonstrated that the expression levels of c-myc and cyclin-D mRNAs increased after FZD7 transfection into HCT-116 cells and a siRNA against FZD7 suppressed c-Myc protein expression (Ueno et al, 2008). Conversely, some Wnt signals were shown to promote viability in some cell types (Almeida et al, 2005;Railo et al, 2008). Wnt signalling through other FZDs might protect our transfectants from apoptosis.…”

Section: Discussionmentioning

confidence: 78%

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

et al. 2009

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BACKGROUND: The canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells. METHODS AND RESULTS: In this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40 -50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (Po0.005), and overall survival was shorter in those patients with higher FZD7 expression (Po0.001). CONCLUSION: These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway.

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Section: Discussionmentioning

confidence: 78%

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

et al. 2009

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“…Since no direct Wnt11 reporters are currently available, we assayed the influence of Cer1 in the control of Wnt11 signalling indirectly by assessing the capacity of Wnt11 to inhibit canonical Wnt signalling as analysed by the Top Flash reporter [56]. Hence, if Cer1 influenced Wnt11 signalling, we would expect to see changes in the Wnt11-mediated inhibition of Top Flash reporter expression [56]. However, Cer1 did not influence the efficiency of Wnt11 in inhibiting Wnt3a-induced Top Flash activity, although it had a notable effect in reducing Wnt3a signalling (Figure 7G).…”

Section: Resultsmentioning

confidence: 99%

“…The monoclonal anti-mouse Cerberus 1 antibody (MAB1986) was from R&D systems, and Western blotting was performed according to Railo et al . [56].…”

Section: Methodsmentioning

confidence: 99%

A Secreted BMP Antagonist, Cer1, Fine Tunes the Spatial Organization of the Ureteric Bud Tree during Mouse Kidney Development

et al. 2011

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The epithelial ureteric bud is critical for mammalian kidney development as it generates the ureter and the collecting duct system that induces nephrogenesis in dicrete locations in the kidney mesenchyme during its emergence. We show that a secreted Bmp antagonist Cerberus homologue (Cer1) fine tunes the organization of the ureteric tree during organogenesis in the mouse embryo. Both enhanced ureteric expression of Cer1 and Cer1 knock out enlarge kidney size, and these changes are associated with an altered three-dimensional structure of the ureteric tree as revealed by optical projection tomography. Enhanced Cer1 expression changes the ureteric bud branching programme so that more trifid and lateral branches rather than bifid ones develop, as seen in time-lapse organ culture. These changes may be the reasons for the modified spatial arrangement of the ureteric tree in the kidneys of Cer1+ embryos. Cer1 gain of function is associated with moderately elevated expression of Gdnf and Wnt11, which is also induced in the case of Cer1 deficiency, where Bmp4 expression is reduced, indicating the dependence of Bmp expression on Cer1. Cer1 binds at least Bmp2/4 and antagonizes Bmp signalling in cell culture. In line with this, supplementation of Bmp4 restored the ureteric bud tip number, which was reduced by Cer1+ to bring it closer to the normal, consistent with models suggesting that Bmp signalling inhibits ureteric bud development. Genetic reduction of Wnt11 inhibited the Cer1-stimulated kidney development, but Cer1 did not influence Wnt11 signalling in cell culture, although it did inhibit the Wnt3a-induced canonical Top Flash reporter to some extent. We conclude that Cer1 fine tunes the spatial organization of the ureteric tree by coordinating the activities of the growth-promoting ureteric bud signals Gndf and Wnt11 via Bmp-mediated antagonism and to some degree via the canonical Wnt signalling involved in branching.

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“…Wnt-11 is best known for its role during development, for example, it is required for convergent extension movements during gastrulation [3] and kidney morphogenesis [4]. In addition, cell-based assays have demonstrated that Wnt-11 promotes cardiac differentiation [5], increases proliferation, migration and transformation of intestinal epithelial cells [6], reduces apoptosis in breast cancer cells [7] and increases cell viability in chinese hamster ovary (CHO) cells [8]. The signals downstream of Wnt-11 are not fully characterised.…”

Section: Introductionmentioning

confidence: 99%

Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

et al. 2010

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BackgroundWnt-11 is a secreted protein that modulates cell growth, differentiation and morphogenesis during development. We previously reported that Wnt-11 expression is elevated in hormone-independent prostate cancer and that the progression of prostate cancer from androgen-dependent to androgen-independent proliferation correlates with a loss of mutual inhibition between Wnt-11- and androgen receptor-dependent signals. However, the prevalence of increased expression of Wnt-11 in patient tumours and the functions of Wnt-11 in prostate cancer cells were not known.ResultsWnt-11 protein levels in prostate tumours were determined by immunohistochemical analysis of prostate tumour tissue arrays. Wnt-11 protein was elevated in 77/117 of tumours when compared with 27 benign prostatic hypertrophy specimens and was present in 4/4 bone metastases. In addition, there was a positive correlation between Wnt-11 expression and PSA levels above 10 ng/ml. Androgen-depleted LNCaP prostate cancer cells form neurites and express genes associated with neuroendocrine-like differentiation (NED), a feature of prostate tumours that have a poor prognosis. Since androgen-depletion increases expression of Wnt-11, we examined the role of Wnt-11 in NED. Ectopic expression of Wnt-11 induced expression of NSE and ASCL1, which are markers of NED, and this was prevented by inhibitors of cyclic AMP-dependent protein kinase, consistent with the known role of this kinase in NED. In contrast, Wnt-11 did not induce NSE expression in RWPE-1 cells, which are derived from benign prostate, suggesting that the role of Wnt-11 in NED is specific to prostate cancer. In addition, silencing of Wnt-11 expression in androgen-depleted LNCaP cells prevented NED and resulted in apoptosis. Silencing of Wnt-11 gene expression in androgen-independent PC3 cells also reduced expression of NSE and increased apoptosis. Finally, silencing of Wnt-11 reduced PC3 cell migration and ectopic expression of Wnt-11 promoted LNCaP cell invasion.ConclusionsThese observations suggest that the increased level of Wnt-11 found in prostate cancer contributes to tumour progression by promoting NED, tumour cell survival and cell migration/invasion, and may provide an opportunity for novel therapy in prostate cancer.

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Wnt-11 signaling leads to down-regulation of the Wnt/β-catenin, JNK/AP-1 and NF-κB pathways and promotes viability in the CHO-K1 cells

Cited by 35 publications

References 66 publications

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

A Secreted BMP Antagonist, Cer1, Fine Tunes the Spatial Organization of the Ureteric Bud Tree during Mouse Kidney Development

Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

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