title: AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway.
abstract: Aldo-keto reductase 1B10 (AKR1B10) is not expressed in normal breast, but upregulated in primary and metastatic breast cancers, being a negative prognostic factor. This study characterized the molecular mechanisms of AKR1B10-promoted breast cancer metastasis. Ectopic expression of AKR1B10 in breast cancer cells MCF-7 and MDA-MB-231 or siRNA-mediated silencing in BT-20 cells affected cell adhesion, migration and invasion in cell culture, and metastasis to the lung in the nude mice through upregulation of integrin α5 and δ-catenin. Silencing of integrin α5 or δ-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. In these cells, the integrin α5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with δ-catenin, stimulated Rac1-mediated cell migration and movement. In human primary and lymph node metastatic breast cancer, AKR1B10, integrin α5 and δ-catenin were correlatively upregulated with r=0.645 (p<0.0001) and r=0.796 (p<0.0001), respectively. These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin α5 and δ-catenin mediated FAK/Src/Rac1 signaling pathway.
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Verhulst
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.|Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: He
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Rao
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.affiliation: China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, 541001, Guangxi, China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.|Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051177:Catenins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D039482:Integrin alpha5; C107953:RAC1 protein, human; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein; D000095002:Delta Catenin
keywords: AKR1B10; Rac1; breast cancer metastasis; integrin α5; δ-catenin