title: Neutral endopeptidase (NEP) is differentially involved in biological activities and cell signaling of colon cancer cell lines derived from various stages of tumor development.
abstract: The presented studies were aimed at exploring the role of neutral endopeptidase (NEP) in the function of colon cancer cell lines LS 180 and SW 620, derived from different grades and stages of tumor development. NEP silencing by siRNA resulted in decreased viability and proliferation accompanied by increased apoptosis in both cell lines. Additionally, cell cycle arrest at the G2/M phase was observed, but only in LS 180 cells. Opposite to these results, serum-stimulated migration was increased in both cell lines. Furthermore, NEP silencing influenced the invasive activity of LS 180 and SW 620 cells in an opposite manner: while LS 180 cells showed an enhanced invasiveness, SW 620 cells exerted a reduced activity. An exploration of the activity of signaling molecules responsible for the function of tumor cells-Akt, PTEN, and FAK-after NEP silencing indicated that the endopeptidase is involved in their regulation. The increased phosphorylation level of Akt was accompanied by a decrease in PTEN in the presence of a high concentration of serum. A reduced concentration of serum did not change the phosphorylation status of Akt. Enhanced autophosphorylation of FAK was observed in LS 180 and SW 620 cells cultivated in a medium with a high concentration of serum. Taken together, these results confirm that NEP is implicated in the regulation of the survival, growth, and motile activity of colon cancer. This is also the first report which shows that NEP mediates cancer cell migration and invasiveness, but not growth and survival, through Akt/FAK signaling pathways.
authors.affiliation: Department of Virology and Immunology, Maria Curie-Sklodowska University, Faculty of Biology and Biotechnology, Akademicka 19 Street, 20-033, Lublin, Poland. magdalena.mizerska-dudka@poczta.umcs.lublin.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mizerska-Kowalska
authors.affiliation: Chair and Department of Clinical Immunology, Medical University of Lublin, W.Chodźki 4a Street, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bojarska-Junak
authors.affiliation: Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Faculty of Biology and Biotechnology, Akademicka 19 Street, 20-033, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakubowicz-Gil
authors.affiliation: Department of Virology and Immunology, Maria Curie-Sklodowska University, Faculty of Biology and Biotechnology, Akademicka 19 Street, 20-033, Lublin, Poland.
authors.forename: Martyna
authors.initials: M
authors.lastname: Kandefer-Szerszeń
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D015260:Neprilysin
keywords: Akt/PTEN; Apoptosis; Cell cycle; Colon cancer; FAK; NEP; Neutral endopeptidase