Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)27293-27304
Number of pages12
Issue number43
Publication statusPublished - 1 Jun 2018

External IDs

PubMed 29930766
ORCID /0000-0002-8691-8423/work/142236128
PubMedCentral PMC6007469
ORCID /0000-0001-9345-026X/work/150328898


Sustainable Development Goals

ASJC Scopus subject areas


  • Frizzled, Prostate cancer, RYK, Wnt receptors, WNT5A

Library keywords