Association of elevated GRP78 expression with increased astrocytoma malignancy via Akt and ERK pathways.
Unlike other members of HSP70 family, GRP78 manifests multifaceted subcellular distribution and forms complex with different signals, resulting in its close correlation with various tumors. However, its expression profile and function in glioma remain less well defined. In this study, normal brain tissue and astrocytic tumor specimens were evaluated for GRP78 expression, which was shown to be up-regulated in astrocytoma compared with normal tissue, increased markedly as astrocytoma pathologic grade escalates, and can still be enhanced for disease recurrence. By employing Cox regression analyses, high GRP78 expression was correlated with a poorer outcome for recurrent glioblastoma patients. In addition, immunofluorescence microscopy detected cell surface positioning of GRP78 on human glioma cells. After transfection with siRNA or antibody ligation of surface GRP78, phosphorylation of Akt and ERK was attenuated. These findings indicate that GRP78 plays an important role in astrocytoma malignancy, whereas its cell surface localization may be attractive for clinical utilization.
Neurosurgical Institute of PLA, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China.
Lu-Hua
LH
Zhang
Xiao-Liang
XL
Yang
Xiang
X
Zhang
Jin-Xiang
JX
Cheng
Wei
W
Zhang
D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002455:Cell Division; D002867:Chromones / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction
D057134:Antibodies, Neutralizing; D002867:Chromones; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D009025:Morpholines; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3