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10.15252/emmm.201708347 http://scihub22266oqcxt.onion/10.15252/emmm.201708347 C5887544!5887544 !29540470     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29540470 &cmd=llinks): Failed to open stream: HTTP request failed! 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Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1 |pdf=|usr=}}{{29540470 }} gab.com Text Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1 JO: EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=29540470 #FOAvip Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self-sufficient form of CRPC Mechanistically, HER2-IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1-mediated cholesterol uptake in SPRY2-deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2-deficient CRPC is dependent on cholesterol bioavailability and SRB1-mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2-deficient CRPC. Twit Text FOAVip Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1 ????EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=29540470 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29540470 #FOAvip English Wikipedia <ref>{{Cite pmid|29540470 }}</ref> Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1 #MMPMID29540470 Patel R ; Fleming J ; Mui E ; Loveridge C ; Repiscak P ; Blomme A ; Harle V ; Salji M ; Ahmad I ; Teo K ; Hamdy FC ; Hedley A ; van den Broek N ; Mackay G ; Edwards J ; Sansom OJ ; Leung HY EMBO Mol Med 2018[Apr]; 10 (4 ): ä PMID29540470 show ga Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self-sufficient form of CRPC Mechanistically, HER2-IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1-mediated cholesterol uptake in SPRY2-deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2-deficient CRPC is dependent on cholesterol bioavailability and SRB1-mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2-deficient CRPC. |Animals [MESH] |Humans [MESH] |Interleukin-6/*metabolism [MESH] |Intracellular Signaling Peptides and Proteins/genetics/*metabolism [MESH] |Male [MESH] |Membrane Proteins/genetics/*metabolism [MESH] |Mice, Nude [MESH] |Phenylenediamines/therapeutic use [MESH] |Prostatic Neoplasms, Castration-Resistant/drug therapy/*metabolism [MESH] |Protein Serine-Threonine Kinases [MESH] |Real-Time Polymerase Chain Reaction [MESH] |Receptor, ErbB-2/genetics/metabolism [MESH] |Receptors, Scavenger/*metabolism [MESH] |Scavenger Receptors, Class B/antagonists & inhibitors [MESH] |Signal Transduction/drug effects/physiology [MESH]Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer (epmc).pdf DeepDyve Pubget Overpricing