title: CT45A1 acts as a new proto-oncogene to trigger tumorigenesis and cancer metastasis.
abstract: Cancer/testis antigen (CTA)-45 family (CT45) belongs to a new family of genes in phylogenetics and is absent in normal tissues except for testis, but is aberrantly overexpressed in various cancer types. Whether CT45 and other CTAs act as proto-oncogenes has not been determined. Using breast cancer as a model, we found that CT45A1, a representative CT45 family member, alone had a weak tumorigenic effect. However, its neoplastic potency was greatly enhanced in the presence of growth factors. Overexpression of CT45A1 in breast cancer cells markedly upregulated various oncogenic and metastatic genes, constitutively activated ERK and CREB signaling pathways, promoted epithelial-mesenchymal transition, and increased cell stemness, tumorigenesis, invasion, and metastasis, whereas silencing CT45A1 significantly reduced cancer cell migration and invasion. We propose that CT45A1 functions as a novel proto-oncogene to trigger oncogenesis and metastasis. CT45A1 and other CT45 members are therefore excellent targets for anticancer drug discovery and targeted tumor therapy, and valuable genes in the study of a molecular phylogenetic tree.
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: B
authors.initials: B
authors.lastname: Shang
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: A
authors.initials: A
authors.lastname: Gao
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Tu
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D009362:Neoplasm Metastasis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; C115163:CREB1 protein, human; C502804:CT45A1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins