title: CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2.
abstract: CD133 is widely expressed in colorectal cancer (CRC) tissues and cell lines. This protein has been used as a marker of CRC cancer stem cells, although the function and mechanism of CD133 in CRC invasion and metastasis remain unclear. In our study, we examined the role of CD133 in CRC invasion in vitro and investigated the mechanism involved in CD133-related invasion. CD133(high) and CD133(low) HCT116 cells were isolated, and the proliferation and invasive ability of these two subpopulations were tested. CD133(high) HCT116 cells exhibited greater proliferation and invasion compared with CD133(low) HCT116 cells. CD133 knockdown (using CD133 small-interfering [si]RNA) inhibited the invasive activity of CD133si-HCT116 cells. For the first time, we found that the expression of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) was down-regulated in CD133si-HCT116 cells. In addition, for the TIMP-2si-HCT116 cells (transfected with TIMP-2 siRNA), in vitro invasion was significantly decreased, whereas the expression of CD133 remained unchanged. Finally, the metalloproteinase 2 and MEK/ERK signaling pathways were examined, and no significant change was observed after the knockdown of CD133 or TIMP-2 in HCT116 cells. In conclusion, we demonstrated that CD133 plays an important role in HCT116 cell invasion, and for the first time, we found that CD133 knockdown significantly down-regulated TIMP-2 expression, which suggests that CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2.
authors.affiliation: Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.forename: Hailiang
authors.initials: H
authors.lastname: Feng
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Bian
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhao
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Yang
authors.forename: Bei
authors.initials: B
authors.lastname: Gu
authors.forename: Zhanwen
authors.initials: Z
authors.lastname: Li
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2