title: The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis.
abstract: Metastasis is a major cause of death in patients with breast cancer. Stathmin1 (STMN1) is a phosphoprotein associated with cancer metastasis. It exhibits a complicated phosphorylation pattern in response to various extracellular signals, but its signaling mechanism is poorly understood. In this study, we report that phosphorylation of STMN1 at Ser25 and Ser38 is necessary to maintain cell migration capabilities and is associated with shorter disease-free survival (DFS) in breast cancer. In addition, we report that glucose-regulated protein of molecular mass 78 (GRP78) is a novel phospho-STMN1 binding protein upon STMN1 Ser25/Ser38 phosphorylation. This phosphorylation-dependent interaction is regulated by MEK kinase and is required for STMN1-GRP78 complex stability and STMN1-mediated migration. We also propose a prognostic model based on phospho-STMN1 and GRP78 to assess metastatic risk in breast cancer patients.
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Breast Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xia-Ying
authors.initials: XY
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: He-Sheng
authors.initials: HS
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi-Zi
authors.initials: YZ
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiao
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: xinhu@fudan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Institutes of Biomedical Science, Fudan University, Shanghai, China. Electronic address: zhimingshao@yahoo.com.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D016016:Proportional Hazards Models; D011485:Protein Binding; D034622:RNA Interference; D018570:Risk Assessment; D012307:Risk Factors; D012694:Serine; D015398:Signal Transduction; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C493995:STMN1 protein, human; D050777:Stathmin; D012694:Serine; D020930:MAP Kinase Kinase Kinases
keywords: Breast cancer; GRP78; Metastasis; Phosphorylation; Stathmin