Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both β-catenin dependent and independent Wnt signalling

Henry, Claire; Quadir, Ashfaque; Hawkins, Nicholas J.; Jary, Eve; Llamosas, Estelle; Kumar, Dhiraj; Daniels, Benjamin; Ward, Robyn L.; Ford, Caroline

doi:10.1007/s00432-014-1824-y

Cited by 66 publications

(74 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…gbx2 is a direct target gene (Li et al, 2009) and ap2alpha is one of the immediate early Wnt/β-catenin responsive genes at the neural plate border (de Crozé et al, 2011). Although Ror2 is a major receptor in β-catenin-independent Wnt signaling, it has also been reported that Ror2 can positively or negatively regulate Wnt/β-catenin signaling depending on the cellular context (Billiard et al, 2005;Green et al, 2007;Henry et al, 2015;Li et al, 2008;Mikels et al, 2009;Mikels and Nusse, 2006;Rasmussen et al, 2013). However, we found that neither lowering nor increasing Wnt/β-catenin activity by overexpression of dnLef or Tcf1, respectively, rescued NPB specification in Ror2-depleted embryos.…”

Section: Discussioncontrasting

confidence: 82%

“…Ror2 has been shown to modulate Wnt/β-catenin signaling and interestingly, both positive and negative regulation of the Wnt/β-catenin pathway has been reported (Billiard et al, 2005;Green et al, 2007;Henry et al, 2015;Li et al, 2008;Mikels and Nusse, 2006;Rasmussen et al, 2013). However, neither inhibition nor activation of Wnt/β-catenin signaling by co-injection of effective doses of dominant-negative (dn)lef1 RNA or tcf1 RNA with Ror2 MO, respectively, rescued the downregulation of msx1 ( Fig.…”

Section: Ror2 Is Required For Neural Crest Induction and Specificatiomentioning

confidence: 90%

See 1 more Smart Citation

Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border

et al. 2016

View full text Add to dashboard Cite

The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

show abstract

Section: Discussioncontrasting

confidence: 82%

Section: Ror2 Is Required For Neural Crest Induction and Specificatiomentioning

confidence: 90%

Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the lung cancer, an aberrant expression and/or alteration of the Wnt signaling components also are observed in 50% of human NSCLC cell lines and lung cancer resected samples [42], in which Wnt signaling is associated with increased proliferation and metastatic properties of lung cancer cells, poor prognosis, and resistances to conventional chemoradiotherapies and targeted therapies in lung cancer patients [14, 33, 43–45]. Of interest, implications of dysregulated noncanonical Wnt signaling and the cancer type-dependent oncogenic or tumor suppressor role of Wnt signaling in tumorigenesis have recently spurred an increasing attention in the metastasis and therapeutic resistances of lung cancer [14, 22, 23, 25, 31, 36, 45–47]. …”

Section: Discussionmentioning

confidence: 99%

“…However, a constitutive expression or increased expression of Wnt5a and its receptor Ror2 is involved in enhanced invasive and metastatic properties of many cancer types, suggesting an oncogenic role of Wnt5a/Ror2 signaling in tumorigenesis [17, 21, 40, 51–54]. In addition to its oncogenic roles in cancers, Wnt5a also has been found to inhibit canonical Wnt/ β -catenin signaling in a Ror2-dependent manner and has a tumor suppressor role in several cancer types, such as colorectal cancer (CRC) [55], thyroid cancer [56], and maybe breast cancers as well [34, 36, 57]. With respect to its antitumor activity, Wnt5a is able to inhibit tumor invasion and metastasis by antagonizing the Wnt/ β -catenin signaling pathway and inducing the degradation of β -catenin [32].…”

Section: Discussionmentioning

confidence: 99%

Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway

Yang

Zhang

et al. 2016

Stem Cells International

View full text Add to dashboard Cite

The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies.

show abstract

“…Yes (19,127,132) Yes (48,133) Breast cancer (81) ; prostate cancer (41) ; melanoma (90,92) ; non-small cell lung cancer (134) ; colorectal cancer (135) ; gastric cancer (136) ; ovarian cancer (131) …”

Section: Ror2mentioning

confidence: 99%

WNT5A and Its Receptors in the Bone-Cancer Dialogue

Thiele

Rachner

Rauner

et al. 2016

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Wnt signaling is critical for tumorigenesis and skeletal remodeling. However, its contribution to the formation of metastatic bone lesions remains poorly defined. One major challenge of unraveling its role in cancer progression is the high complexity of Wnt signaling, which includes numerous ligands, receptors, and inhibitors, with intricate biological effects and specific signaling pathways depending on the cellular context. In this perspective, we summarize the role of the noncanonical Wnt ligand WNT5A in the development and metastatic process of osteotropic cancer entities. We focus on its tumor-suppressive function in breast cancer, tumor promoting effects in melanoma, and ambiguous role in prostate cancer, and discuss potential challenges and opportunities that may be associated with targeting Wnt signaling for cancer therapy and treatment of bone metastases.

show abstract

Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both β-catenin dependent and independent Wnt signalling

Cited by 66 publications

References 18 publications

Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border

Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border

Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway

WNT5A and Its Receptors in the Bone-Cancer Dialogue

Contact Info

Product

Resources

About