WNT5A and Its Receptors in the Bone-Cancer Dialogue

Thiele, Stefanie; Rachner, Tilman D.; Rauner, Martina; Hofbauer, Lorenz C.

doi:10.1002/jbmr.2899

Cited by 13 publications

(8 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that cells of cancer 4 cluster had high-level expression of FZD1 which interacted with the receptor WNT5A of monocytes (Fig. 3I, J), and the ligand-receptor complex of FZD1/WNT5A played a key role in cancer cells by promoting the proliferation and differentiation of monocytes into osteoclasts [36] ( Fig. 3I, J).…”

Section: Identification Of the Potential Evolution Process In The Bonmentioning

confidence: 91%

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Pan¹,

Zhang²,

Xu³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Background: Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy. Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python. Results: A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC. Conclusion: The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.

show abstract

Section: Identification Of the Potential Evolution Process In The Bonmentioning

confidence: 91%

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Pan¹,

Zhang²,

Xu³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Furthermore, there is an abundant release of TGF-β and vascular endothelial growth factor (VEGF) by the cancer cells, which directly affect the osteoblast activity [ 45 ]. This is done through the WNT pathway, which is implicated in osteoblastogenesis [ 46 , 47 , 48 ]. The combination of this WNT pathway upregulation coupled with the reported decreased expression of the WNT antagonist, dikkopf-1, in patients with advanced prostate cancer is associated with the formation of osteoblastic lesions ( Figure 1 b) [ 49 ].…”

Section: Biology Of Bone Metastasismentioning

confidence: 99%

Emerging and Established Models of Bone Metastasis

Jinnah

Zacks

Gwam

et al. 2018

Cancers

View full text Add to dashboard Cite

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. Bone is the primary site of metastasis for several cancers—breast and prostate cancers in particular. Efforts to treat bone metastases have been stymied by a lack of models to study the progression, cellular players, and signaling pathways driving bone metastasis. In this review, we examine newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic, and in silico computational bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cells enter and then escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

show abstract

“…Recent studies identified WNT5A to interact with various members of the FZD family (FZD2, 3, 4, 7, 8) as well as the co-receptors ROR2 and RYK [ 7 ]. Moreover, WNT5A and its receptors have been implicated in different human cancer entities including glioblastoma, leukemia, and pancreatic cancer [ 17 – 23 ]. After having previously shown that WNT5A exerts potent anti-tumor effects in prostate cancer cells [ 5 ], this study aimed to investigate which of the receptors mediates its anti-tumor effects.…”

Section: Introductionmentioning

confidence: 99%

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

Prostate cancer is the most common malignancy in men and has a high propensity to metastasize to bone. WNT5A has recently been implicated in the progression of prostate cancer, however, the receptors that mediate its effects remain unknown. Here, we identified Wnt receptors that are highly expressed in prostate cancer and investigated which of these receptors mediate the anti-tumor effects of WNT5A in prostate cancer in vitro.Extensive in vitro analyses revealed that the WNT5A receptors FZD5 and RYK mediate the anti-tumor effects of WNT5A on prostate cancer cells. Knock-down of FZD5 completely abrogated the anti-proliferative effect of WNT5A in PC3 cells. In contrast, knock-down of RYK and FZD8 did not rescue the inhibition of proliferation after WNT5A overexpression. In contrast, RYK knock-down inhibited the pro-apoptotic effect of WNT5A in PC3 cells by 60%, whereas the knock-down of either FZD5 or FZD8 further stimulated apoptosis after WNT5A overexpression (by 33% and 234%, respectively). Surface plasmon resonance analysis indicated that WNT5A has a 30% stronger binding response to FZD5 than to RYK. Further investigations using a tissue microarray revealed that expression of RYK is increased in advanced prostate cancer tumor stages, but is not associated with survival of prostate cancer patients. In contrast, patients with low local FZD5 expression, in particular in combination with low WNT5A expression, showed a longer disease-specific survival.In conclusion, WNT5A/FZD5 and WNT5A/RYK signaling are both involved in mediating the pro-apoptotic and anti-proliferative effects of WNT5A in prostate cancer.

show abstract

WNT5A and Its Receptors in the Bone-Cancer Dialogue

Cited by 13 publications

References 134 publications

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Emerging and Established Models of Bone Metastasis

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

Contact Info

Product

Resources

About