title: Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer.
abstract: Smoothened (Smo) is a G protein-coupled receptor protein encoded by the Smo gene of the hedgehog signalling pathway, which is thought to play an important role in maintaining organ patterning, cell differentiation and self-renewal. The possible role of Smo in the process of tumorigenesis and metastasis of breast cancer still remains unclear. The present experiments were to investigate the effect of Smo on activating breast cancer stem-like CD44(+)CD24(-) cells and the tumorigenesis and metastasis of breast cancer. By injected CD44(+)CD24(-) cells (1×10(4)) into the cleared fat pad of NOD/SCID mice, it was observed that CD44(+)CD24(-) cells possess higher tumor-initiating capacity and metastasis properties than equal numbers of non-CD44(+)CD24(-) cells. The mRNA and protein expressions of Smo in CD44(+)CD24(-) cells were higher than those in non-CD44(+)CD24(-) cells, indicating that Smo may play a role in maintaining breast cancer stem cell features. qRT-PCR results revealed that expressions of STAT3, Bcl-2 and cyclinD1 mRNA in MCF-7 cells were decreased after transfected by Smo siRNA. In addition, the expressions of MMP-2 and MMP-9 were downregulated in MCF-7 cells after Smo expression was inhibited. Smo inhibition may be a possible therapeutic target that potentially suppresses breast tumor formation and development.
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Pathology, Medical College of Dalian University, Dalian, Liaoning Province, China.
authors.forename: Le
authors.initials: L
authors.lastname: Kang
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Fan
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, Liaoning Province, China. Electronic address: lilianhong917@126.com.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Medical College of Dalian University, Dalian, Liaoning Province, China. Electronic address: sabrinatao@sina.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Tao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D000072086:Smoothened Receptor
chemical_list: D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor
keywords: Breast cancer stem-like cells; Metastasis; Smoothened (Smo); Tumorigenesis