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10.1158/2159-8290.CD-14-1507 http://scihub22266oqcxt.onion/10.1158/2159-8290.CD-14-1507 C4456212!4456212 !25829424     free     free     free Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 259.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 259.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25829424 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cancer+Discov 2015 ; 5 (6 ): 652-67 Nephropedia Template TP {{tp|p=25829424 |t=2015. HIF2?-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma |pdf=|usr=}}{{25829424 }} gab.com Text HIF2 -Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma JO: Cancer Discov http://www.kidney.de/pget.php?&tw=1&pmid=25829424 #FOAvip Two hallmarks of clear-cell renal cell carcinoma (ccRCC) are constitutive hypoxia-inducible factor (HIF) signaling and abundant intracellular lipid droplets (LD). However, regulation of lipid storage and its role in ccRCC are incompletely understood. Transcriptional profiling of primary ccRCC samples revealed that expression of the LD coat protein gene PLIN2 was elevated in tumors and correlated with HIF2?, but not HIF1?, activation. HIF2?-dependent PLIN2 expression promoted lipid storage, proliferation, and viability in xenograft tumors. Mechanistically, lipid storage maintained integrity of the endoplasmic reticulum (ER), which is functionally and physically associated with LDs. Specifically, PLIN2-dependent lipid storage suppressed cytotoxic ER stress responses that otherwise result from elevated protein synthetic activity characteristic of ccRCC cells. Thus, in addition to promoting ccRCC proliferation and anabolic metabolism, HIF2? modulates lipid storage to sustain ER homeostasis, particularly under conditions of nutrient and oxygen limitation, thereby promoting tumor cell survival. SIGNIFICANCE: We demonstrate that HIF2? promotes lipid storage, ER homeostasis, and cell viability in ccRCC via upregulation of the LD coat protein PLIN2, revealing a novel function for the well-documented "clear-cell" phenotype and identifying ER stress as a targetable vulnerability created by HIF2?/PLIN2 suppression in this common renal malignancy. Twit Text FOAVip HIF2 -Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma ????Cancer Discov http://www.kidney.de/pget.php?&tw=1&pmid=25829424 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25829424 #FOAvip English Wikipedia <ref>{{Cite pmid|25829424 }}</ref> HIF2?-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma #MMPMID25829424 Qiu B ; Ackerman D ; Sanchez DJ ; Li B ; Ochocki JD ; Grazioli A ; Bobrovnikova-Marjon E ; Diehl JA ; Keith B ; Simon MC Cancer Discov 2015[Jun]; 5 (6 ): 652-67 PMID25829424 show ga Two hallmarks of clear-cell renal cell carcinoma (ccRCC) are constitutive hypoxia-inducible factor (HIF) signaling and abundant intracellular lipid droplets (LD). However, regulation of lipid storage and its role in ccRCC are incompletely understood. Transcriptional profiling of primary ccRCC samples revealed that expression of the LD coat protein gene PLIN2 was elevated in tumors and correlated with HIF2?, but not HIF1?, activation. HIF2?-dependent PLIN2 expression promoted lipid storage, proliferation, and viability in xenograft tumors. Mechanistically, lipid storage maintained integrity of the endoplasmic reticulum (ER), which is functionally and physically associated with LDs. Specifically, PLIN2-dependent lipid storage suppressed cytotoxic ER stress responses that otherwise result from elevated protein synthetic activity characteristic of ccRCC cells. Thus, in addition to promoting ccRCC proliferation and anabolic metabolism, HIF2? modulates lipid storage to sustain ER homeostasis, particularly under conditions of nutrient and oxygen limitation, thereby promoting tumor cell survival. SIGNIFICANCE: We demonstrate that HIF2? promotes lipid storage, ER homeostasis, and cell viability in ccRCC via upregulation of the LD coat protein PLIN2, revealing a novel function for the well-documented "clear-cell" phenotype and identifying ER stress as a targetable vulnerability created by HIF2?/PLIN2 suppression in this common renal malignancy. |*Homeostasis [MESH] |*Lipid Metabolism [MESH] |Animals [MESH] |Basic Helix-Loop-Helix Transcription Factors/*metabolism [MESH] |Carcinoma, Renal Cell/genetics/*metabolism/pathology [MESH] |Cell Line, Tumor [MESH] |Cell Survival/genetics [MESH] |Disease Models, Animal [MESH] |Drug Resistance, Neoplasm/genetics [MESH] |Endoplasmic Reticulum Stress [MESH] |Endoplasmic Reticulum/*metabolism [MESH] |Gene Expression [MESH] |Gene Expression Regulation, Neoplastic [MESH] |Heterografts [MESH] |Humans [MESH] |Kidney Neoplasms/genetics/*metabolism/pathology [MESH] |Membrane Proteins/genetics/metabolism [MESH] |Mice [MESH] |Oncogenes [MESH] |Perilipin-2 [MESH] |Protein Biosynthesis [MESH] |Tumor Burden [MESH]HIF2?-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostas(epmc).pdf DeepDyve Pubget Overpricing