PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis.
Studies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial stem cells. Equivalent cell populations are thought to exist in the human intestine; however robust and specific protein markers are lacking. Here, we show that in the human...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797055733904179200 |
|---|---|
| author | Sakthianandeswaren, A Christie, M D'Andreti, C Tsui, C Jorissen, R Li, S Fleming, N Gibbs, P Lipton, L Malaterre, J Ramsay, R Phesse, T Ernst, M Jeffery, R Poulsom, R Leedham, S Segditsas, S Tomlinson, I Bernhard, O Simpson, R Walker, F Faux, M Church, N Catimel, B Flanagan, D |
| author_facet | Sakthianandeswaren, A Christie, M D'Andreti, C Tsui, C Jorissen, R Li, S Fleming, N Gibbs, P Lipton, L Malaterre, J Ramsay, R Phesse, T Ernst, M Jeffery, R Poulsom, R Leedham, S Segditsas, S Tomlinson, I Bernhard, O Simpson, R Walker, F Faux, M Church, N Catimel, B Flanagan, D |
| author_sort | Sakthianandeswaren, A |
| collection | OXFORD |
| description | Studies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial stem cells. Equivalent cell populations are thought to exist in the human intestine; however robust and specific protein markers are lacking. Here, we show that in the human small and large intestine, PHLDA1 is expressed in discrete crypt base and some position +4 cells. In small adenomas, PHLDA1 was expressed in a subset of undifferentiated and predominantly Ki-67-negative neoplastic cells, suggesting that a basic hierarchy of differentiation is retained in early tumorigenesis. In large adenomas, carcinomas, and metastases PHLDA1 expression became widespread, with increased expression and nuclear localization at invasive margins. siRNA-mediated suppression of PHLDA1 in colon cancer cells inhibited migration and anchorage-independent growth in vitro and tumor growth in vivo. The integrins ITGA2 and ITGA6 were downregulated in response to PHLDA1 suppression, and accordingly cell adhesion to laminin and collagen was significantly reduced. We conclude that PHLDA1 is a putative epithelial stem cell marker in the human small and large intestine and contributes to migration and proliferation in colon cancer cells. |
| first_indexed | 2024-03-06T19:14:01Z |
| format | Journal article |
| id | oxford-uuid:17bb0863-971d-45be-852e-7fb36de069d7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:14:01Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:17bb0863-971d-45be-852e-7fb36de069d72022-03-26T10:39:11ZPHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:17bb0863-971d-45be-852e-7fb36de069d7EnglishSymplectic Elements at Oxford2011Sakthianandeswaren, AChristie, MD'Andreti, CTsui, CJorissen, RLi, SFleming, NGibbs, PLipton, LMalaterre, JRamsay, RPhesse, TErnst, MJeffery, RPoulsom, RLeedham, SSegditsas, STomlinson, IBernhard, OSimpson, RWalker, FFaux, MChurch, NCatimel, BFlanagan, DStudies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial stem cells. Equivalent cell populations are thought to exist in the human intestine; however robust and specific protein markers are lacking. Here, we show that in the human small and large intestine, PHLDA1 is expressed in discrete crypt base and some position +4 cells. In small adenomas, PHLDA1 was expressed in a subset of undifferentiated and predominantly Ki-67-negative neoplastic cells, suggesting that a basic hierarchy of differentiation is retained in early tumorigenesis. In large adenomas, carcinomas, and metastases PHLDA1 expression became widespread, with increased expression and nuclear localization at invasive margins. siRNA-mediated suppression of PHLDA1 in colon cancer cells inhibited migration and anchorage-independent growth in vitro and tumor growth in vivo. The integrins ITGA2 and ITGA6 were downregulated in response to PHLDA1 suppression, and accordingly cell adhesion to laminin and collagen was significantly reduced. We conclude that PHLDA1 is a putative epithelial stem cell marker in the human small and large intestine and contributes to migration and proliferation in colon cancer cells. |
| spellingShingle | Sakthianandeswaren, A Christie, M D'Andreti, C Tsui, C Jorissen, R Li, S Fleming, N Gibbs, P Lipton, L Malaterre, J Ramsay, R Phesse, T Ernst, M Jeffery, R Poulsom, R Leedham, S Segditsas, S Tomlinson, I Bernhard, O Simpson, R Walker, F Faux, M Church, N Catimel, B Flanagan, D PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title | PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title_full | PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title_fullStr | PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title_full_unstemmed | PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title_short | PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. |
| title_sort | phlda1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis |
| work_keys_str_mv | AT sakthianandeswarena phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT christiem phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT dandretic phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT tsuic phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT jorissenr phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT lis phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT flemingn phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT gibbsp phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT liptonl phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT malaterrej phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT ramsayr phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT phesset phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT ernstm phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT jefferyr phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT poulsomr phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT leedhams phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT segditsass phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT tomlinsoni phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT bernhardo phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT simpsonr phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT walkerf phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT fauxm phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT churchn phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT catimelb phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis AT flanagand phlda1expressionmarkstheputativeepithelialstemcellsandcontributestointestinaltumorigenesis |