title: Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell growth and induces apoptosis in vitro and in nude mouse xenografts.
abstract: The transcription factor specificity protein 1 (Sp1) plays a role in the development and progression of various types of human cancers, while cancer stem cells (CSCs) are important in cancer cell self-renewal, resistance to chemotherapy and metastatic potential. This study investigated the role of Sp1 in colon CSC growth and apoptosis. Colon CSCs were successfully enriched using special culture medium and identified by typical CSC gene expression. In a quiescent state, these CSCs formed spheres with slow proliferation; overexpressed Sp1, CD44, CD166 and CD133 proteins; upregulated mesenchymal markers; and a downregulated epithelial marker were noted. In ex vivo experiments, the Sp1 protein was expressed in 74.8% of colon cancer tissues, whereas it was expressed only in 42.2% of the distant normal colon mucosae. Furthermore, inhibition of SP1 expression using Sp1 siRNA or mithramycin A (MIT) led to marked suppression of CSC growth and induced apoptosis. In addition, the percentage of CD44+/CD166+ cells was significantly downregulated both in vivo and in vitro following Sp1 inhibition. In conclusion, Sp1 suppression attenuated the characteristics of colon CSCs. Thus, Sp1 inhibition may be potentially useful for the future development of a novel therapeutic strategy to control colon cancer.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Tianming
authors.initials: T
authors.lastname: Cheng
authors.forename: Fachao
authors.initials: F
authors.lastname: Zhi
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jide
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
mesh_terms: D000071916:AC133 Antigen; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000096:biosynthesis; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006023:Glycoproteins / Q000096:biosynthesis; D045325:HCT116 Cells; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000071916:AC133 Antigen; D020410:Activated-Leukocyte Cell Adhesion Molecule; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; C066851:mithramycin A; D008926:Plicamycin