| Added by | standudu |
|---|---|
| Last modified by | mollevi |
| Group name | EquipeCTCS |
| Item Type | Journal Article |
| Title | Autocrine secretion of progastrin promotes the survival and self-renewal of colon cancer stem-like cells |
| Creator | Giraud et al. |
| Author | J. Giraud |
| Author | L. M. Failla |
| Author | J. M. Pascussi |
| Author | E. L. Lagerqvist |
| Author | J. Ollier |
| Author | P. Finetti |
| Author | F. Bertucci |
| Author | C. Ya |
| Author | I. Gasmi |
| Author | J. F. Bourgaux |
| Author | M. Prudhomme |
| Author | T. Mazard |
| Author | I. Ait-Arsa |
| Author | L. Houhou |
| Author | D. Birnbaum |
| Author | A. Pelegrin |
| Author | C. Vincent |
| Author | J. G. Ryall |
| Author | D. Joubert |
| Author | J. Pannequin |
| Author | F. Hollande |
| Abstract | Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and post-treatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer (CRC), where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in regulating CSC phenotype in advanced CRC. Progastrin expression and secretion were highly enriched in colon CSC isolated from human CRC cell lines and colon tumor biopsies. Progastrin expression promoted CSC self-renewal and survival, whereas its depletion by RNAi-mediated or antibody-mediated strategies altered the homeostatic proportions of CSC cells within heterogeneous CRC tumors. Progastrin downregulation also decreased the frequency of ALDHhigh cells, impairing their tumor-initiating potential, and inhibited the high glycolytic activity of ALDHhigh CSC to limit their self-renewal capability. Taken together, our results show how colorectal CSC maintain their tumor-initiating and self-renewal capabilities by secreting progastrin, thereby contributing to the tumor microenvironment to support malignancy. |
| Publication | Cancer Res |
| Date | May 4 2016 |
| Journal Abbr | Cancer research |
| DOI | 10.1158/0008-5472.CAN-15-1497 |
| ISSN | 1538-7445 (Electronic) 0008-5472 (Linking) |
| Date Added | 2018/11/14 - 15:24:46 |
| Date Modified | 2018/11/14 - 15:24:46 |
| Notes and Attachments | (Note) (Note) 27197176 (Attachment) |
Institut de Recherche en Cancérologie de
