caa a22 4500 606235175 CHVBK 20210128101241.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2204-2 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2204-2 GRP78 promotes the invasion of pancreatic cancer cells by FAK and JNK [Elektronische Daten] [X. Yuan, Ming Dong, Xin Li, J. Zhou] The major characteristics of pancreatic cancer are its excessive local invasion and early systemic dissemination. The glucose-regulated protein is over-expressed in many human cancers including pancreatic cancer and correlated with invasion and metastasis in many cancers. To investigate the effect of Grp78 on the invasion of pancreatic cancer, we used western blot and Transwell assay. We found Grp78 is expressed at lower levels in capan-2 and higher expressed in MiaPaCa-2 cells, and Grp78 expression levels were correlated with the invasion potentials of tumor cells. Then,we increased the expression of Grp78 in capan-2 cells and decreased the expression of Grp78 in MiaPaCa-2 cells. We found that over-expression of Grp78 caused significant increase in the expression of TIMP-1, TIMP-2, MMP-14, MMP-2, and MMP-9 in Capan-2 cells. Consistently, knockdown of Grp78 decreased the expression of them in MiaPaCa-2 cells. Gelatin zymography showed Grp78 over-expression stimulated the activities of MMP-2 and MMP-9, while GRP78 knockdown reduced the activities of MMP-2 and MMP-9. Cytoskeleton staining showed that knockdown of Grp78 caused a marked increase in cytoskeleton F-actin stress fibers in MiaPaCa-2 cells. Consistently, GRP78 knockdown hyperactivated RhoA and inhibited significantly Rac activity. Grp78 over-expression decreases the RhoA and stimulated Rac activity. We also found that Grp78 modulated FAK and JNK signaling pathways. Over-expression of GRP78 in Capan-2 activated FAK and JNK. Finally, we demonstrated that knockdown of FAK by shRNA in combination with blockade of JNK signaling pathway with SP600125 completely inhibited GRP78-induced cancer cell invasion. GRP78 is involved in the regulation of pancreatic cancer invasion. FAK and JNK are the key downstream effectors of GRP78. Springer Science+Business Media New York, 2014 GRP78 nationallicence FAK nationallicence JNK nationallicence Pancreatic cancer nationallicence Invasion and metastasis nationallicence Yuan X. Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut Dong Ming Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut Li Xin Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut Zhou J. Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 55-62 0300-8177 398:1-2<55 2015 398 11010 https://doi.org/10.1007/s11010-014-2204-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2204-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yuan X. Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut NATIONALLICENCE 700 1- Dong Ming Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut NATIONALLICENCE 700 1- Li Xin Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut NATIONALLICENCE 700 1- Zhou J. Gastrointestinal Surgery Department, First Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning Province, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 55-62 0300-8177 398:1-2<55 2015 398 11010