FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2159314503> ?p ?o ?g. }

• W2159314503 abstract "Abstract Background Bone loss and pathological fractures are common skeletal complications associated with androgen deprivation therapy and bone metastases in prostate cancer patients. We have previously demonstrated that prostate cancer cells secrete receptor activator of NF-kB ligand (RANKL), a protein essential for osteoclast differentiation and activation. However, the mechanism(s) by which RANKL is produced remains to be determined. The objective of this study is to gain insight into the molecular mechanisms controlling RANKL expression in metastatic prostate cancer cells. Results We show here that phosphorylation of Smad 5 by integrin αvβ3 and RUNX2 by CD44 signaling, respectively, regulates RANKL expression in human-derived PC3 prostate cancer cells isolated from bone metastasis. We found that RUNX2 intranuclear targeting is mediated by phosphorylation of Smad 5. Indeed, Smad5 knock-down via RNA interference and inhibition of Smad 5 phosphorylation by an αv inhibitor reduced RUNX2 nuclear localization and RANKL expression. Similarly, knockdown of CD44 or RUNX2 attenuated the expression of RANKL. As a result, conditioned media from these cells failed to support osteoclast differentiation in vitro. Immunohistochemistry analysis of tissue microarray sections containing primary prostatic tumor (grade2-4) detected predominant localization of RUNX2 and phosphorylated Smad 5 in the nuclei. Immunoblotting analyses of nuclear lysates from prostate tumor tissue corroborate these observations. Conclusions Collectively, we show that CD44 signaling regulates phosphorylation of RUNX2. Localization of RUNX2 in the nucleus requires phosphorylation of Smad-5 by integrin αvβ3 signaling. Our results suggest possible integration of two different pathways in the expression of RANKL. These observations imply a novel mechanistic insight into the role of these proteins in bone loss associated with bone metastases in patients with prostate cancer." @default.
• W2159314503 created "2016-06-24" @default.
• W2159314503 creator A5014501396 @default.
• W2159314503 creator A5016146359 @default.
• W2159314503 creator A5081505598 @default.
• W2159314503 date "2012-09-11" @default.
• W2159314503 modified "2023-10-18" @default.
• W2159314503 title "Integrin αvβ3 and CD44 pathways in metastatic prostate cancer cells support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-κB ligand signaling axis" @default.
• W2159314503 cites W1266576439 @default.
• W2159314503 cites W171027393 @default.
• W2159314503 cites W1967379035 @default.
• W2159314503 cites W1969960083 @default.
• W2159314503 cites W1973265846 @default.
• W2159314503 cites W1978401958 @default.
• W2159314503 cites W1979860021 @default.
• W2159314503 cites W1982670166 @default.
• W2159314503 cites W1983304896 @default.
• W2159314503 cites W1983932174 @default.
• W2159314503 cites W1984736888 @default.
• W2159314503 cites W1987317889 @default.
• W2159314503 cites W1988268462 @default.
• W2159314503 cites W1989718024 @default.
• W2159314503 cites W1992168421 @default.
• W2159314503 cites W1995470316 @default.
• W2159314503 cites W1996575870 @default.
• W2159314503 cites W1998643392 @default.
• W2159314503 cites W2003404796 @default.
• W2159314503 cites W2008073344 @default.
• W2159314503 cites W2009495556 @default.
• W2159314503 cites W2009943239 @default.
• W2159314503 cites W2012675589 @default.
• W2159314503 cites W2014688699 @default.
• W2159314503 cites W2019898510 @default.
• W2159314503 cites W2019998985 @default.
• W2159314503 cites W2023082041 @default.
• W2159314503 cites W2028968731 @default.
• W2159314503 cites W2039384987 @default.
• W2159314503 cites W2042125973 @default.
• W2159314503 cites W2042778072 @default.
• W2159314503 cites W2048285476 @default.
• W2159314503 cites W2048299560 @default.
• W2159314503 cites W2050618607 @default.
• W2159314503 cites W2057097813 @default.
• W2159314503 cites W2057570836 @default.
• W2159314503 cites W2064615925 @default.
• W2159314503 cites W2066845679 @default.
• W2159314503 cites W2070678884 @default.
• W2159314503 cites W2073246990 @default.
• W2159314503 cites W2074645605 @default.
• W2159314503 cites W2074760000 @default.
• W2159314503 cites W2081449873 @default.
• W2159314503 cites W2084842783 @default.
• W2159314503 cites W2086008590 @default.
• W2159314503 cites W2092233035 @default.
• W2159314503 cites W2097934124 @default.
• W2159314503 cites W2098846399 @default.
• W2159314503 cites W2105834006 @default.
• W2159314503 cites W2107277218 @default.
• W2159314503 cites W2112076644 @default.
• W2159314503 cites W2112523271 @default.
• W2159314503 cites W2116386904 @default.
• W2159314503 cites W2117721992 @default.
• W2159314503 cites W2120004034 @default.
• W2159314503 cites W2121551386 @default.
• W2159314503 cites W2124664018 @default.
• W2159314503 cites W2125560549 @default.
• W2159314503 cites W2128843508 @default.
• W2159314503 cites W2135463143 @default.
• W2159314503 cites W2139777018 @default.
• W2159314503 cites W2143904769 @default.
• W2159314503 cites W2146994889 @default.
• W2159314503 cites W2153801209 @default.
• W2159314503 cites W2154419328 @default.
• W2159314503 cites W2156681756 @default.
• W2159314503 cites W2156920440 @default.
• W2159314503 cites W2157518260 @default.
• W2159314503 cites W2168257649 @default.
• W2159314503 cites W4236053983 @default.
• W2159314503 doi "https://doi.org/10.1186/1476-4598-11-66" @default.
• W2159314503 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3499378" @default.
• W2159314503 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22966907" @default.
• W2159314503 hasPublicationYear "2012" @default.
• W2159314503 type Work @default.
• W2159314503 sameAs 2159314503 @default.
• W2159314503 citedByCount "68" @default.
• W2159314503 countsByYear W21593145032013 @default.
• W2159314503 countsByYear W21593145032014 @default.
• W2159314503 countsByYear W21593145032015 @default.
• W2159314503 countsByYear W21593145032016 @default.
• W2159314503 countsByYear W21593145032017 @default.
• W2159314503 countsByYear W21593145032018 @default.
• W2159314503 countsByYear W21593145032019 @default.
• W2159314503 countsByYear W21593145032020 @default.
• W2159314503 countsByYear W21593145032021 @default.
• W2159314503 countsByYear W21593145032022 @default.
• W2159314503 countsByYear W21593145032023 @default.
• W2159314503 crossrefType "journal-article" @default.
• W2159314503 hasAuthorship W2159314503A5014501396 @default.
• W2159314503 hasAuthorship W2159314503A5016146359 @default.
• W2159314503 hasAuthorship W2159314503A5081505598 @default.

• next