| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling |
| Creator | Prévostel et al. |
| Author | Corinne Prévostel |
| Author | Cyrine Rammah-Bouazza |
| Author | Hélène Trauchessec |
| Author | Lucile Canterel-Thouennon |
| Author | Muriel Busson |
| Author | Marc Ychou |
| Author | Philippe Blache |
| Abstract | SOX9 inactivation is frequent in colorectal cancer (CRC) due to SOX9 gene mutations and/or to ectopic expression of MiniSOX9, a dominant negative inhibitor of SOX9. In the present study, we report a heterozygous L142P inactivating mutation of SOX9 in the DLD-1 CRC cell line and we demonstrate that the conditional expression of a wild type SOX9 in this cell line inhibits cell growth, clonal capacity and colonosphere formation while decreasing both the activity of the oncogenic Wnt/ß-catenin signaling pathway and the expression of the c-myc oncogene. This activity does not require SOX9 transcriptional function but, rather, involves an interaction of SOX9 with nuclear ß-catenin. Furthermore, we report that SOX9 inhibits tumor development when conditionally expressed in CRC cells injected either subcutaneous or intraperitoneous in BALB/c mice as an abdominal metastasis model. These observations argue in favor of a tumor suppressor activity for SOX9. As an siRNA targeting SOX9 paradoxically also inhibits DLD-1 and HCT116 CRC cell growth, we conclude that there is a critical level of endogenous active SOX9 needed to maintain CRC cell growth. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 50 |
| Pages | 82228-82243 |
| Date | Dec 13, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.10573 |
| ISSN | 1949-2553 |
| Library Catalog | PubMed |
| Extra | PMID: 27429045 PMCID: PMC5347687 |
| Tags | Animals, beta Catenin, c-myc inhibition, Cell Proliferation, colorectal cancer, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, HCT116 Cells, Heterozygote, Humans, Mice, Inbred BALB C, Mutation, original, Peritoneal Neoplasms, Proto-Oncogene Proteins c-myc, RNA Interference, SOX9, SOX9 Transcription Factor, Time Factors, Transfection, Tumor Burden, tumor suppressor, Wnt Signaling Pathway, Wnt/ß-catenin inhibition |
| Date Added | 2018/11/13 - 17:25:59 |
| Date Modified | 2019/05/21 - 14:33:20 |
Institut de Recherche en Cancérologie de
