title: Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis.
abstract: Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133(+) population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Shih-Pei
authors.initials: SP
authors.lastname: Lin
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Lee
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Miller
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000071916:AC133 Antigen; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006023:Glycoproteins / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; D055551:HSP27 Heat-Shock Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D054648:Protein Phosphatase 2