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10.1038/onc.2017.64 http://scihub22266oqcxt.onion/10.1038/onc.2017.64 C5532065!5532065!28346424     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Oncogene 2017 ; 36 (30): 4299-310 Nephropedia Template TP {{tp|p=28346424|t=2017. Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist |pdf=|usr=}}{{28346424}} gab.com Text Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist JO: Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=28346424 #FOAvip Castration-resistant prostate cancer (CRPC) remains a major clinical challenge due to the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance towards hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC. In transgenic adenocarcinoma mouse prostate model, Skp2 depletion leads to a profound repression of prostate tumor growth and distal metastasis and substantially prolonged overall survival. We revealed that Skp2 regulates CRPC through Twist-mediated oncogenic functions including epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) acquisitions. Mechanistically, Skp2 interacted with Twist and promoted the non-degradative ubiquitination of Twist. Consequently, Skp2 stabilized Twist protein expression by preventing proteasomal degradation of Twist by ?-TrCP. We found that Twist overexpression augments CSC self-renewal and population and that Skp2 inhibition reverts Twist?s effects on CSC regulation. Furthermore, genetically depleting or pharmacologically inactivating Skp2 synergistically re-sensitized CRPC cells towards chemotherapies such as paclitaxel or doxorubicin. Together, the current study uncovering Skp2-mediated Twist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumor progression. It provides prove-of principle that Skp2 targeting is a promising approach to combat metastatic CRPC by targeting Twist and CSCs. Twit Text FOAVip Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist ????Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=28346424 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28346424 #FOAvip English Wikipedia <ref>{{Cite pmid|28346424}}</ref> Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist #MMPMID28346424 Ruan D; He J; Li CF; Lee HJ; Liu J; Lin HK; Chan CH Oncogene 2017[Jul]; 36 (30): 4299-310 PMID28346424show ga Castration-resistant prostate cancer (CRPC) remains a major clinical challenge due to the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance towards hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC. In transgenic adenocarcinoma mouse prostate model, Skp2 depletion leads to a profound repression of prostate tumor growth and distal metastasis and substantially prolonged overall survival. We revealed that Skp2 regulates CRPC through Twist-mediated oncogenic functions including epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) acquisitions. Mechanistically, Skp2 interacted with Twist and promoted the non-degradative ubiquitination of Twist. Consequently, Skp2 stabilized Twist protein expression by preventing proteasomal degradation of Twist by ?-TrCP. We found that Twist overexpression augments CSC self-renewal and population and that Skp2 inhibition reverts Twist?s effects on CSC regulation. Furthermore, genetically depleting or pharmacologically inactivating Skp2 synergistically re-sensitized CRPC cells towards chemotherapies such as paclitaxel or doxorubicin. Together, the current study uncovering Skp2-mediated Twist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumor progression. It provides prove-of principle that Skp2 targeting is a promising approach to combat metastatic CRPC by targeting Twist and CSCs. äSkp2 deficiency restricts the progression and stem cell features of ca(epmc).pdf DeepDyve Pubget Overpricing