title: Cell Surface GRP78 Accelerated Breast Cancer Cell Proliferation and Migration by Activating STAT3.
abstract: High levels of cell surface glucose regulated protein 78 (sGRP78) have been implicated in cancer growth, survival, metastasis, and chemotherapy resistance. However, the underlying mechanism remains largely unknown. Here we report that the level of sGRP78 expression in human breast tumors gradually increases during cancer progression. Overexpression of GRP78 significantly enhanced its membrane distribution in human MCF-7 breast cancer cells, but had no effect on endoplasmic reticulum (ER) stress. High levels of sGRP78 facilitated cell proliferation and migration, as well as suppressed cell apoptosis. Neutralization of sGRP78 by a specific antibody against GRP78 alleviated sGRP78-induced cell growth and migration. Importantly, high phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) were found in human breast tumors that express sGRP78 and MCF-7 cells infected with adenovirus encoding human GRP78. Pretreatment with a GRP78 antibody suppressed STAT3 phosphorylation. Furthermore, genetic and pharmacological inhibition of STAT3 reversed the impacts of GRP78 on cell proliferation, apoptosis, and migration. These findings indicate that STAT3 mediates sGRP78-promoted breast cancer cell growth and migration.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Clinical Pathology, The First People's Hospital of Lianyungang, Lianyungang, 222000, Jiangsu Province, China; Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, Hubei Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, Hubei Province, China.
authors.forename: Changhua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D050796:STAT3 Transcription Factor / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D057134:Antibodies, Neutralizing; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human