title: Dysregulation of apoptotic signaling pathways by interaction of RPLP0 and cathepsin X/Z in gastric cancer.
abstract: Cathepsin X (CTSX, also called cathepsin Z/P) is a cysteine protease that still plays an unknown role in human cancer. It has been shown to bind cell surface heparin sulphate proteoglycans and integrins, indicating possible functions of CTSX in cellular adhesion, phagocytosis, and immune response. Our previous studies have shown an association between Helicobacter pylori (H. pylori) infection, a strong up-regulation of CTSX, and development of gastric cancer. In this study, yeast two-hybrid analysis revealed that RPLP0, a ribosomal protein P0, interacts with the human CTSX protein in gastric cancer. The CTSX/RPLP0 interaction was confirmed by co-immunoprecipitation assays. In addition, co-localization studies in cancer cell line N87 and gastric cancer tissue samples were performed. Laserscan microscopy revealed a shuttling of RPLP0 (and CTSX) from cytoplasm to the nucleus after CTSX knockdown. Down-regulation of RPLP0 resulted in G1 arrest of gastric cancer cells, whereas knockdown of CTSX led to G1 arrest and apoptosis after 48 h. Knockdown of both proteins caused increased apoptosis. RPLP0 deficiency could suppress cell growth and cell cycle progression by down-regulating CDK2. It was further demonstrated that RPLP0 affected p21 expression, but did not change the expression of Cyclin E. Down-regulation of both proteins at least through CDK2 suggests an anti-apoptotic effect on gastric cancer cells and opens up new possibilities for apoptotic immune modulation and gastric cancer therapy.
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Teller
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Doerthe
authors.initials: D
authors.lastname: Jechorek
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hartig
authors.affiliation: Institute of Biometry and Medical Informatics, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Adolf
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reißig
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany. Electronic address: sabine.franke@med.ovgu.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Franke
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D056663:Cathepsin Z / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D012269:Ribosomal Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D012269:Ribosomal Proteins; C054675:ribosomal protein P0; D056663:Cathepsin Z
keywords: Apoptosis; Cathepsin X; Gastric cancer; Ribosomal phosphoprotein P0 (RPLP0); Yeast two-hybrid