title: Overexpression of KiSS-1 reduces colorectal cancer cell invasion by downregulating MMP-9 via blocking PI3K/Akt/NF-κB signal pathway.
abstract: Metastasis of colorectal cancer (CRC) depends critically on MMP-9. KiSS-1 is a human malignant melanoma metastasis-suppressor gene. Thus, the interaction between MMP-9 and KiSS-1 has drawn considerable attention in recent years. In the present study, it was hypothesized that KiSS-1 gene could repress the metastatic potential of colorectal cancer cells by inhibiting the expression of MMP-9. Stable transfection of KiSS-1 specific siRNA and KiSS-1 expression vector in human CRC cell line HCT-116 was achieved by lentivirus infection. Moreover, the cell proliferation, invasiveness, and apoptosis were evaluated by CCK-8 method, transwell experiment, and fluorescence activated cell sorter, respectively. We also investigated the expression of MMP-9, PI3K, Akt, pAKt, and NF-кB subunit p65 using western blotting. KiSS-1 overexpression significantly decreased the cell proliferation and invasiveness of HCT-119 cells, while apoptosis was enhanced. The result of western blotting showed that synthesis of MMP-9, PI3K, p65, and phosphorylation of Akt were significantly blocked by overexpression of KiSS-1. Concatenated treatment of KiSS-1 overexpression vector with PI3K and Akt agonists attenuated the effect of KiSS-1 on the biological activity of CRC cells and also released the expression of MMP-9, PI3K, p65, and phosphorylation of Akt from the influence of overexpression of KiSS-1. Overexpression of KiSS-1 suppressed the invasiveness of CRC cells, and the gene exerted its function by reducing the expression of MMP-9 via blocking of tge PI3K/Akt/NF-κB pathway.
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors: Shaoqin
authors: S
authors: Chen
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors: Wei
authors: W
authors: Chen
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors: Xiang
authors: X
authors: Zhang
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors: Suyong
authors: S
authors: Lin
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors: Zhihua
authors: Z
authors: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D059648:Kisspeptins / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D051996:Transcription Factor RelA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9