title: Cyclin D1b splice variant promotes αvβ3-mediated adhesion and invasive migration of breast cancer cells.
abstract: Cyclin D1b, a splice variant of the cell cycle regulator cyclin D1, holds oncogenic functions in human cancer. However, the mechanisms underlying cyclin D1b function remain poorly understood. Here we introduced wild-type cyclin D1a or cyclin D1b variant into non-metastatic MCF-7 cells. Our results show that ectopic expression of cyclin D1b promotes invasiveness of the cancer cells in a cyclin D1a independent manner. Specifically, cyclin D1b is found to modulate the expression of αvβ3, which characterizes the metastatic phenotype, and enhance tumor cell invasive potential in cooperating with HoxD3. Notably, cyclin D1b promotes αvβ3-mediated adhesion and invasive migration, which are associated with invasive potential of breast cancer cells. Further exploration indicates that cyclin D1b makes breast cancer cells more sensitive to toll-like receptor 4 ligand released from damaged tumor cells. These findings reveal a role of cyclin D1b as a possible mediator of αvβ3 transcription to promote tumor metastasis.
authors.affiliation: Department of Physiology, Hubei University of Chinese Medcine, Wuhan 430065, China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wu
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Luo
authors.affiliation: Department of Physiology, Hubei University of Chinese Medcine, Wuhan 430065, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Hubei University of Chinese Medcine, Wuhan 430065, China.
authors.forename: Qiu-Xiao
authors.initials: QX
authors.lastname: Zhan
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China. Electronic address: fengzhg@public.wh.hb.cn.
authors.forename: Zuo-Hua
authors.initials: ZH
authors.lastname: Feng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010641:Phenotype; D020033:Protein Isoforms; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; D018398:Homeodomain Proteins; C061248:ITGB3 protein, human; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D008024:Ligands; D020033:Protein Isoforms; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014157:Transcription Factors; C073547:HOXA4 protein, human; D019938:Cyclin D1
keywords: Breast cancer; Cyclin D1b; HoxD3; Invasion; αvβ3-integrin