| PHLDA1 Expression Marks the Putative Epithelial Stem Cells and Contributes to Intestinal Tumorigenesis. | |
| | |
MedLine Citation:
|
PMID: 21558389 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
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. Cancer Res; 71(10); 1-11. ©2011 AACR. |
| | |
Authors:
|
Anuratha Sakthianandeswaren; Michael Christie; Carla D'Andreti; Cary Tsui; Robert N Jorissen; Shan Li; Nicholas I Fleming; Peter Gibbs; Lara Lipton; Jordane Malaterre; Robert G Ramsay; Toby J Phesse; Matthias Ernst; Rosemary E Jeffery; Richard Poulsom; Simon J Leedham; Stefania Segditsas; Ian P M Tomlinson; Oliver K Bernhard; Richard J Simpson; Francesca Walker; Maree C Faux; Nicole Church; Bruno Catimel; Dustin J Flanagan; Elizabeth Vincan; Oliver M Sieber |
Related Documents
:
|
8879269 - Dna damage in exfoliated buccal cells of smokers assessed by the single cell gel electr... 20004969 - Effect of functionalised fluorescence-labelled nanoparticles on mesenchymal stem cell d... 7053559 - Phagocytosis: flow cytometric quantitation with fluorescent microspheres. 9667509 - Attachment staining: a novel method for flow cytometric quantitation of protein express... 15584019 - Chemical cytometry for monitoring metabolism of a ras-mimicking substrate in single cells. 2127179 - Aneuploid and polyploid cellular dna heterogeneity in insect cell material of diptera s... 7902009 - Physiological desensitization of beta 3-adrenergic responses in brown fat cells: involv... 8290579 - Tat-mediated delivery of heterologous proteins into cells. 7153249 - Reactivation of intestinal epithelial cell brush border motility: atp-dependent contrac... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-10 |
Journal Detail:
|
Title: Cancer research Volume: - ISSN: 1538-7445 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-11 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Authors' Affiliations: Ludwig Institute for Cancer Research, Department of Medical Oncology, Royal Melbourne Hospital; Faculty of Medicine, Dentistry and Health Sciences, Department of Surgery, and Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia; Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; London Research Institute, Cancer Research UK, London, United Kingdom; and Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lin...
Next Document: Systemic DNA damage related to cancer.