title: Upregulation of the growth arrest-specific-2 in recurrent colorectal cancers, and its susceptibility to chemotherapy in a model cell system.
abstract: Colorectal cancer (CRC) is one of the most common life-threatening malignances worldwide. CRC relapse markedly decreases the 5-year survival of patients following surgery. Aberrant expression of genes involved in pathways regulating the cell cycle, cell proliferation, or cell death are frequently reported in CRC tumorigenesis. We hypothesized that genes involved in CRC relapse might serve as prognostic indicators. We first evaluated the significance of gene sequences in the feces of patients with CRC relapse by consulting a public database. Tumorigenesis of target tissues was tested through tumor cell growth, cell cycle regulation, and chemotherapeutic efficacy. We found a highly significant correlation between CRC relapse and growth arrest-specific 2 (GAS2) gene expression. Based on cell models, the overexpressed GAS2 was associated with cellular growth rate, cell cycle regulation, and with chemotherapeutic sensitivity. Cell division was impaired by treating cells with 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid (XK469), even when the cells were overexpressing GAS2. Thus, downregulation of GAS2 expression might control CRC relapse after curative resection. GAS2 could serve as a noninvasive marker from the feces of patients with prediagnosed CRC. Our findings suggest that GAS2 could have potential clinical applications for predicting early CRC relapse after radical resection, and that XK469 might impair tumor cell division by reducing GAS2 expression or blocking its cellular translocation. This will help in selecting the best therapeutic option, 5-fluorouracil in combination with XK469, for patients overexpressing GAS2 in CRC cells. Thus, GAS2 might act as a prognostic biomolecule and potential therapeutic target in patients with CRC relapse.
authors.affiliation: Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
authors.forename: Chia-Long
authors.initials: CL
authors.lastname: Lee
authors.affiliation: Department of Surgery, Taipei-Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chien
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Breast Center, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Ching Kuo Institute of Management and Health, Keelung, Taiwan; Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei, Taiwan.
authors.forename: Ruey-Neng
authors.initials: RN
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ccchangcmri@gmail.com.
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C490936:GAS2 protein, human; D008840:Microfilament Proteins