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10.18632/oncotarget.24090 http://scihub22266oqcxt.onion/10.18632/oncotarget.24090 C5884641!5884641 !29643986     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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29643986 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncotarget 2018 ; 9 (21 ): 15464-15479 Nephropedia Template TP {{tp|p=29643986 |t=2018. Ajuba receptor mediates the internalization of tumor-secreted GRP78 into macrophages through different endocytosis pathways |pdf=|usr=}}{{29643986 }} gab.com Text Ajuba receptor mediates the internalization of tumor-secreted GRP78 into macrophages through different endocytosis pathways JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=29643986 #FOAvip Glucose-regulated protein 78 (GRP78), an ER chaperone, is overexpressed in cancer cells. Solid tumor cells can secrete GRP78 that can promote tumor angiogenesis, differentiation of bone marrow-derived mesenchymal stem cells, tumor cell proliferation and polarization of tumor-associated macrophages. However, the mechanism by which GRP78 functions as a tumor promoter either by staying on the membrane to stimulate intracellular signals or directly entering into cytosolic remains unknown. Here, we reported that an endotoxin-free His-GRP78 protein was purified in vitro that simulates original secreted GRP78. Through analyzing GRP78 concentration in serum samples from 32 colon cancer patients, 40 nM His-GRP78 was selected as an optimized dose to treat cells. Biochemical analysis revealed that secreted GRP78 was able to enter into RAW264.7 and THP-1 cells directly rather than stay on the plasma membrane to transfer signals. Further studies showed that GRP78 internalization was endocytosis-dependent, and both phagocytosis and clathrin, caveolin-1 and micropinocytosis-mediated endocytosis pathways contributed to internalization of secreted GRP78 into cells. Mechanistically, Ajuba is able to interact with GRP78. Ablation of Ajuba suppressed the internalization of secreted GRP78 into cells, indicating that Ajuba was responsible for internalization of secreted GRP78 into RAW264.7. Furthermore, we observed that internalized GRP78 could entered into the mitochondrion and endoplasmic reticulum, which provided a suitable place and enough time for GRP78 to function in molecular and cellular processes. Together, these results reveal a novel mechanism by which secreted GRP78 internalizes into macrophages in the tumor microenvironment, which provides a potential target for drug development. Twit Text FOAVip Ajuba receptor mediates the internalization of tumor-secreted GRP78 into macrophages through different endocytosis pathways ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=29643986 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29643986 #FOAvip English Wikipedia <ref>{{Cite pmid|29643986 }}</ref> Ajuba receptor mediates the internalization of tumor-secreted GRP78 into macrophages through different endocytosis pathways #MMPMID29643986 La X ; Zhang L ; Li H ; Li Z ; Song G ; Yang P ; Yang Y Oncotarget 2018[Mar]; 9 (21 ): 15464-15479 PMID29643986 show ga Glucose-regulated protein 78 (GRP78), an ER chaperone, is overexpressed in cancer cells. Solid tumor cells can secrete GRP78 that can promote tumor angiogenesis, differentiation of bone marrow-derived mesenchymal stem cells, tumor cell proliferation and polarization of tumor-associated macrophages. However, the mechanism by which GRP78 functions as a tumor promoter either by staying on the membrane to stimulate intracellular signals or directly entering into cytosolic remains unknown. Here, we reported that an endotoxin-free His-GRP78 protein was purified in vitro that simulates original secreted GRP78. Through analyzing GRP78 concentration in serum samples from 32 colon cancer patients, 40 nM His-GRP78 was selected as an optimized dose to treat cells. Biochemical analysis revealed that secreted GRP78 was able to enter into RAW264.7 and THP-1 cells directly rather than stay on the plasma membrane to transfer signals. Further studies showed that GRP78 internalization was endocytosis-dependent, and both phagocytosis and clathrin, caveolin-1 and micropinocytosis-mediated endocytosis pathways contributed to internalization of secreted GRP78 into cells. Mechanistically, Ajuba is able to interact with GRP78. Ablation of Ajuba suppressed the internalization of secreted GRP78 into cells, indicating that Ajuba was responsible for internalization of secreted GRP78 into RAW264.7. Furthermore, we observed that internalized GRP78 could entered into the mitochondrion and endoplasmic reticulum, which provided a suitable place and enough time for GRP78 to function in molecular and cellular processes. Together, these results reveal a novel mechanism by which secreted GRP78 internalizes into macrophages in the tumor microenvironment, which provides a potential target for drug development. äAjuba receptor mediates the internalization of tumor-secreted GRP78 in(epmc).pdf DeepDyve Pubget Overpricing