Matches in SemOpenAlex for { <https://semopenalex.org/work/W2969553668> ?p ?o ?g. }
- W2969553668 endingPage "1704" @default.
- W2969553668 startingPage "1692" @default.
- W2969553668 abstract "WNT signaling is implicated in embryonic development, and in adult tissue homeostasis, while its deregulation is evident in disease. This study investigates the unique roles of canonical WNT10B in both normal prostate development and prostate cancer (PCa) progression.Organ culture and rat ventral prostates (VPs) were used to study Wnt10b ontogeny and growth effect of WNT10B protein. PB-SV40 LTag rat VPs were utilized for Wnt expression polymerase chain reaction (PCR) array and immunohistochemistry. Human localized PCa tissue microarrays (TMAs) were investigated for differential WNT10B expression. Human RNA-seq data sets were queried for differential expression of WNT10B in metastatic and localized PCa. Knockdown of WNT10B in PC3 cells was utilized to study its effects on proliferation, stemness, epithelial to mesenchymal transition (EMT), and xenograft propagation.Wnt10b expression was highest at birth and rapidly declined in the postnatal rat VP. Exogenous WNT10B addition to culture developing VPs decreased growth suggesting an antiproliferative role. VPs from PB-SV40 LTag rats with localized PCa showed a 25-fold reduction in Wnt10b messenger RNA (mRNA) expession, confirmed at the protein level. Human PCa TMAs revealed elevated WNT10B protein in prostate intraepithelial neoplasia compared with normal prostates but reduced levels in localized PCa specimens. In contrast, RNA-seq data set of annotated human PCa metastasis found a significant increase in WNT10B mRNA expression compared with localized tumors suggesting stage-specific functions of WNT10B. Similarly, WNT10B mRNA levels were increased in metastatic cell lines PC3, PC3M, as well as in HuSLC, a PCa stem-like cell line, as compared with disease-free primary prostate epithelial cells. WNT10B knockdown in PC3 cells reduced expression of EMT genes, MMP9 and stemness genes NANOG and SOX2 and markedly reduced the stem cell-like side population. Furthermore, loss of WNT10B abrogated the ability of PC3 cells to propagate tumors via serial transplantation.Taken together, these results suggest a dual role for WNT10B in normal development and in PCa progression with opposing functions depending on disease stage. We propose that decreased WNT10B levels in localized cancer allow for a hyperproliferative state, whereas increased levels in advanced disease confer a stemness and malignant propensity which is mitigated by knocking down WNT10B levels. This raises the potential for WNT10B as a novel target for therapeutic intervention in metastatic PCa." @default.
- W2969553668 created "2019-08-29" @default.
- W2969553668 creator A5000735599 @default.
- W2969553668 creator A5007731416 @default.
- W2969553668 creator A5029667495 @default.
- W2969553668 creator A5049719845 @default.
- W2969553668 creator A5067845778 @default.
- W2969553668 creator A5086448556 @default.
- W2969553668 creator A5091473418 @default.
- W2969553668 date "2019-08-21" @default.
- W2969553668 modified "2023-10-16" @default.
- W2969553668 title "The role of WNT10B in normal prostate gland development and prostate cancer" @default.
- W2969553668 cites W1026221944 @default.
- W2969553668 cites W1578291413 @default.
- W2969553668 cites W1794768501 @default.
- W2969553668 cites W189173739 @default.
- W2969553668 cites W1965948654 @default.
- W2969553668 cites W1971039813 @default.
- W2969553668 cites W1974810481 @default.
- W2969553668 cites W1975298077 @default.
- W2969553668 cites W1984667218 @default.
- W2969553668 cites W1994734085 @default.
- W2969553668 cites W2007236609 @default.
- W2969553668 cites W2013464193 @default.
- W2969553668 cites W2013885638 @default.
- W2969553668 cites W2021064276 @default.
- W2969553668 cites W2026579311 @default.
- W2969553668 cites W2029094183 @default.
- W2969553668 cites W2030013561 @default.
- W2969553668 cites W2030193055 @default.
- W2969553668 cites W2038569449 @default.
- W2969553668 cites W2042965279 @default.
- W2969553668 cites W2051663511 @default.
- W2969553668 cites W2053548194 @default.
- W2969553668 cites W2064988924 @default.
- W2969553668 cites W2069381736 @default.
- W2969553668 cites W2073998126 @default.
- W2969553668 cites W2074288765 @default.
- W2969553668 cites W2077690851 @default.
- W2969553668 cites W2080761866 @default.
- W2969553668 cites W2089704952 @default.
- W2969553668 cites W2097240638 @default.
- W2969553668 cites W2107277218 @default.
- W2969553668 cites W2108075096 @default.
- W2969553668 cites W2109193598 @default.
- W2969553668 cites W2136810701 @default.
- W2969553668 cites W2138305197 @default.
- W2969553668 cites W2141681777 @default.
- W2969553668 cites W2144680000 @default.
- W2969553668 cites W2154430204 @default.
- W2969553668 cites W2156802024 @default.
- W2969553668 cites W2192080449 @default.
- W2969553668 cites W2395086704 @default.
- W2969553668 cites W2396961956 @default.
- W2969553668 cites W2626821385 @default.
- W2969553668 cites W2754574141 @default.
- W2969553668 cites W2757722557 @default.
- W2969553668 cites W2799978578 @default.
- W2969553668 cites W2901278462 @default.
- W2969553668 cites W2910159078 @default.
- W2969553668 cites W2923668295 @default.
- W2969553668 cites W3022010626 @default.
- W2969553668 doi "https://doi.org/10.1002/pros.23894" @default.
- W2969553668 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31433503" @default.
- W2969553668 hasPublicationYear "2019" @default.
- W2969553668 type Work @default.
- W2969553668 sameAs 2969553668 @default.
- W2969553668 citedByCount "14" @default.
- W2969553668 countsByYear W29695536682020 @default.
- W2969553668 countsByYear W29695536682021 @default.
- W2969553668 countsByYear W29695536682022 @default.
- W2969553668 countsByYear W29695536682023 @default.
- W2969553668 crossrefType "journal-article" @default.
- W2969553668 hasAuthorship W2969553668A5000735599 @default.
- W2969553668 hasAuthorship W2969553668A5007731416 @default.
- W2969553668 hasAuthorship W2969553668A5029667495 @default.
- W2969553668 hasAuthorship W2969553668A5049719845 @default.
- W2969553668 hasAuthorship W2969553668A5067845778 @default.
- W2969553668 hasAuthorship W2969553668A5086448556 @default.
- W2969553668 hasAuthorship W2969553668A5091473418 @default.
- W2969553668 hasBestOaLocation W29695536682 @default.
- W2969553668 hasConcept C104317684 @default.
- W2969553668 hasConcept C105580179 @default.
- W2969553668 hasConcept C121608353 @default.
- W2969553668 hasConcept C137620995 @default.
- W2969553668 hasConcept C142724271 @default.
- W2969553668 hasConcept C173396325 @default.
- W2969553668 hasConcept C203014093 @default.
- W2969553668 hasConcept C204232928 @default.
- W2969553668 hasConcept C2776235491 @default.
- W2969553668 hasConcept C2779013556 @default.
- W2969553668 hasConcept C2780192828 @default.
- W2969553668 hasConcept C502942594 @default.
- W2969553668 hasConcept C54355233 @default.
- W2969553668 hasConcept C55493867 @default.
- W2969553668 hasConcept C62478195 @default.
- W2969553668 hasConcept C71924100 @default.
- W2969553668 hasConcept C81885089 @default.