PMID- 23764754 OWN - NLM STAT- MEDLINE DCOM- 20140122 LR - 20211021 IS - 1460-2180 (Electronic) IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 34 IP - 11 DP - 2013 Nov TI - IMP1 promotes tumor growth, dissemination and a tumor-initiating cell phenotype in colorectal cancer cell xenografts. PG - 2647-54 LID - 10.1093/carcin/bgt217 [doi] AB - Igf2 mRNA binding protein 1 (IMP1, CRD-BP, ZBP-1) is a messenger RNA binding protein that we have shown previously to regulate colorectal cancer (CRC) cell growth in vitro. Furthermore, increased IMP1 expression correlates with enhanced metastasis and poor prognosis in CRC patients. In the current study, we sought to elucidate IMP1-mediated functions in CRC pathogenesis in vivo. Using CRC cell xenografts, we demonstrate that IMP1 overexpression promotes xenograft tumor growth and dissemination into the blood. Furthermore, intestine-specific knockdown of Imp1 dramatically reduces tumor number in the Apc (Min/+) mouse model of intestinal tumorigenesis. In addition, IMP1 knockdown xenografts exhibit a reduced number of tumor cells entering the circulation, suggesting that IMP1 may directly modulate this early metastatic event. We further demonstrate that IMP1 overexpression decreases E-cadherin expression, promotes survival of single tumor cell-derived colonospheres and promotes enrichment and maintenance of a population of CD24+CD44+ cells, signifying that IMP1 overexpressing cells display evidence of loss of epithelial identity and enhancement of a tumor-initiating cell phenotype. Taken together, these findings implicate IMP1 as a modulator of tumor growth and provide evidence for a novel role of IMP1 in early events in CRC metastasis. FAU - Hamilton, Kathryn E AU - Hamilton KE AD - Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Noubissi, Felicite K AU - Noubissi FK FAU - Katti, Prateek S AU - Katti PS FAU - Hahn, Christopher M AU - Hahn CM FAU - Davey, Sonya R AU - Davey SR FAU - Lundsmith, Emma T AU - Lundsmith ET FAU - Klein-Szanto, Andres J AU - Klein-Szanto AJ FAU - Rhim, Andrew D AU - Rhim AD FAU - Spiegelman, Vladimir S AU - Spiegelman VS FAU - Rustgi, Anil K AU - Rustgi AK LA - eng GR - F32 DK093207-01/DK/NIDDK NIH HHS/United States GR - P30 DK050306/DK/NIDDK NIH HHS/United States GR - CA153102/CA/NCI NIH HHS/United States GR - T32 DK007066/DK/NIDDK NIH HHS/United States GR - P30 CA014520/CA/NCI NIH HHS/United States GR - AR063361/AR/NIAMS NIH HHS/United States GR - K08 DK088945/DK/NIDDK NIH HHS/United States GR - R01 DK056645-12/DK/NIDDK NIH HHS/United States GR - P30 CA016520/CA/NCI NIH HHS/United States GR - U01 DK085551/DK/NIDDK NIH HHS/United States GR - R01 AR063361/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130612 PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Adenomatous Polyposis Coli Protein) RN - 0 (IMP1 protein, mouse) RN - 0 (RNA-Binding Proteins) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Adenomatous Polyposis Coli Protein/*physiology MH - Animals MH - Apoptosis MH - Blotting, Western MH - Cell Adhesion MH - Cell Differentiation MH - Cell Movement MH - Cell Proliferation MH - Cell Transformation, Neoplastic/metabolism/*pathology MH - Colorectal Neoplasms/metabolism/*pathology MH - Embryo, Mammalian/metabolism/pathology MH - Epithelial-Mesenchymal Transition MH - Fibroblasts/metabolism/pathology MH - Heterografts MH - Humans MH - Immunoenzyme Techniques MH - Integrases/metabolism MH - Intestinal Mucosa/metabolism MH - Intestines/*pathology MH - Mice MH - Mice, Nude MH - Neoplasm Metastasis MH - Neoplastic Cells, Circulating/metabolism/pathology MH - Neoplastic Stem Cells/metabolism/*pathology MH - Phenotype MH - RNA-Binding Proteins/*physiology MH - Tumor Cells, Cultured PMC - PMC3810836 EDAT- 2013/06/15 06:00 MHDA- 2014/01/23 06:00 PMCR- 2014/11/01 CRDT- 2013/06/15 06:00 PHST- 2013/06/15 06:00 [entrez] PHST- 2013/06/15 06:00 [pubmed] PHST- 2014/01/23 06:00 [medline] PHST- 2014/11/01 00:00 [pmc-release] AID - bgt217 [pii] AID - 10.1093/carcin/bgt217 [doi] PST - ppublish SO - Carcinogenesis. 2013 Nov;34(11):2647-54. doi: 10.1093/carcin/bgt217. Epub 2013 Jun 12.