title: The co-stimulatory molecule B7-H3 promotes the epithelial-mesenchymal transition in colorectal cancer.
abstract: B7-H3, first recognized as a co-stimulatory molecule, is abnormally expressed in cancer tissues and is associated with cancer metastasis and a poor prognosis. However, as an initial event of metastasis, the relationship between the Epithelial-Mesenchymal Transition (EMT ) in cancer cells and B7-H3 has still not been investigated. In this study, we first analyzed B7-H3 expression by immunohistochemistry in colorectal cancer tissues. B7-H3 was expressed in the cancer cell membrane and was associated with the T stage of colorectal cancer; it also showed a positive correlation with MMP2 and MMP9 expression in cancer tissues. Over-expression of B7-H3 in SW480 cells allowed cancer cells to invade and metastasize more than the control cells, whereas invasion and metastasis capabilities were decreased after B7-H3 was knocked down in Caco-2 cells. We further showed that B7-H3 down-regulated the expression of E-cadherin and β-catenin and up-regulated N-cadherin and Vimentin expression, implying that B7-H3 promoted the EMT in colorectal cancer cells. We also checked another character of the EMT, the stemness of cancer cells. CD133, CD44 and Oct4 were significantly elevated after the SW480 cells were transfected with B7-H3 and reduced in Caco-2 cells after B7-H3 was inhibited. In subsequent studies, we proved that B7-H3 upregulated the expression of Smad1 via PI3K-Akt. In conclusion, B7-H3 promotes the EMT in colorectal cancer cells by activating the PI3K-Akt pathway and upregulating the expression of Smad1.
authors.affiliation: Department of Medical Oncology, Beijing Institute of Translational Medicine, Chinese Academy of Sciences/Cancer Center, Aviation General Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Zhangzhang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Beijing Institute of Translational Medicine, Chinese Academy of Sciences/Cancer Center, Aviation General Hospital, Beijing, China.
authors.forename: Hanping
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Department of Nuclear-Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
mesh_terms: D000368:Aged; D000818:Animals; D060887:B7 Antigens / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; D015820:Cadherins; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: B7-H3; Immune response; Immunity; Immunology and Microbiology Section; co-stimulatory molecule; colorectal cancer; epithelial-mesenchymal transition; metastasis