L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer

Boo, Yoon Jung; Park, Joong Min; Kim, Jin; Chae, Yang Seok; Min, Byung Wook; Um, Jun Won; Moon, Hong Young

doi:10.1245/s10434-006-9281-8

Cited by 106 publications

(97 citation statements)

References 22 publications

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“…Development 137 (14) which are involved in cell proliferation and tumorigenesis in the gut (Boo et al, 2007;Pinto et al, 2003;Zeilstra et al, 2008). All three genes were significantly upregulated in intestinal epithelial cells isolated from mutants as compared with control epithelium: Cd44 was upregulated more than 10-fold (Fig.…”

Section: Research Articlementioning

confidence: 98%

N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation

et al. 2010

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SUMMARYWe conditionally substituted E-cadherin (E-cad; cadherin 1) with N-cadherin (N-cad; cadherin 2) during intestine development by generating mice in which an Ncad cDNA was knocked into the Ecad locus. Mutant mice were born, demonstrating that N-cad can structurally replace E-cad and establish proper organ architecture. After birth, mutant mice gradually developed a mutant phenotype in both the small and large intestine and died at ~2-3 weeks of age, probably due to malnutrition during the transition to solid food. Molecular analysis revealed an extended domain of cells from the crypt into the villus region, with nuclear localization of -catenin (-cat; Ctnnb1) and enhanced expression of several -cat target genes. In addition, the BMP signaling pathway was suppressed in the intestinal epithelium of the villi, suggesting that N-cad might interfere with BMP signaling in the intestinal epithelial cell layer. Interestingly, mutant mice developed severe dysplasia and clusters of cells with neoplastic features scattered along the crypt-villus axis in the small and large intestine. Our experimental model indicates that, in the absence of E-cad, the sole expression of N-cad in an epithelial environment is sufficient to induce neoplastic transformations.

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Section: Research Articlementioning

confidence: 98%

N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation

et al. 2010

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“…Subsequent work has shown overexpression of L1CAM in a variety of human tumours, in which it is associated with bad prognosis and metastases formation (Thies et al, 2002;Fogel et al, 2003a, b;Boo et al, 2007;Kaifi et al, 2007). Furthermore, L1CAM was detected in tumour-associated endothelium (Issa et al, 2009;Maddaluno et al, 2009).…”

Section: Introductionmentioning

confidence: 98%

L1CAM–integrin interaction induces constitutive NF-κB activation in pancreatic adenocarcinoma cells by enhancing IL-1β expression

et al. 2010

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L1 cell adhesion molecule (L1CAM) overexpression is often associated with bad prognosis in various human carcinomas. Recent studies also suggest a role of L1CAM in pancreatic ductal adenocarcinomas (PDAC). To further address its contribution, we expressed functional domains of L1CAM in PT45-P1 PDAC cells. We found that L1CAM that is full length (L1-FL), but neither the soluble ectodomain (L1ecto) nor the cytoplasmic part (L1cyt), could enhance cell proliferation or tumour growth in mice. Expression of L1-FL resulted in constitutive activation of NF-jB, which was abolished by L1CAM knockdown. We showed that the expression of IL-1b was selectively upregulated by L1-FL, and increased IL-1b levels were instrumental for sustained NF-jB activation. IL-1b production and NF-jB activation were abolished by knockdown of a5-integrin and integrin-linked kinase, but insensitive to depletion of L1CAM cleavage proteinases. Supporting these data, PT45-P1 cells transduced with an L1CAM mutant deficient in integrin binding (L1-RGE) did not support the described L1-FL functions. Our results suggest that membranous L1CAM interacts with RGD-binding integrins, leading to sustained NF-jB activation by IL-1b production and autocrine/paracrine signalling. The unravelling of this novel mechanism sheds new light on the important role of L1CAM expression in PDAC cells.

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“…Besides L1CAM expression in neuronal cells, overexpression of L1CAM is observed in various cancer entities such as melanoma, ovarian cancer, colon cancer, and PDAC (19)(20)(21)(22) and the expression of L1CAM correlates with poor prognosis and short survival times. Furthermore, it was noted that L1CAM can be associated with cell growth, cell migration and chemoresistance in tumor cells (20,(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Binding of the transcription factor Slug to the L1CAM promoter is essential for transforming growth factor-β1 (TGF-β)-induced L1CAM expression in human pancreatic ductal adenocarcinoma cells

Schäfer¹

2010

Int J Oncol

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Abstract. Members of the Slug/Snail family of transcription factors are thought to drive epithelial-mesenchymal-transition (EMT) in preneoplastic epithelial cells, thereby contributing to malignant transformation. One mediator in the EMT of pancreatic ductal adenocarcinoma (PDAC) cells and a potential target gene of Slug is the cellular adhesion molecule L1CAM. Using the human pancreatic ductal epithelial cell line H6c7 and the PDAC cell line Panc1, we could show that along with TGF-ß1-induced EMT, L1CAM expression is increased in a Slug-but not Snail-dependent fashion. Two E-box recognition motifs in the L1CAM promoter upstream of the most distal transcriptional start site could be verified by gel shift and supershift assay to interact with Slug. ChIP assays detected an increased interaction of Slug with both recognition motifs of the human L1CAM promoter in TGF-ß1-treated H6c7 cells, whereas binding of Snail was downregulated. Moreover, ChIP assays with Panc1 cells confirmed this interaction of Slug with the human L1CAM promoter and further detected an interaction of both recognition sites with RNA-polymerase II in a Slug-dependent fashion. Luciferase reporter gene assays using wild-type or singleand double-mutated variants of the L1CAM promoter confirmed transcriptional activation by Slug involving both recognition motifs. By demonstrating the direct transcriptional control of L1CAM expression through Slug during TGF-ß1-induced EMT of PDAC cells, our findings point to a novel mechanism by which Slug contributes quite early to tumorigenesis. Moreover, our study is the first one describing the control of the human L1CAM promoter in tumor cells.

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L1 Expression as a Marker for Poor Prognosis, Tumor Progression, and Short Survival in Patients with Colorectal Cancer

Abstract: L1 expression is associated with tumor progression and poor survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

Cited by 106 publications

References 22 publications

N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation

N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation

L1CAM–integrin interaction induces constitutive NF-κB activation in pancreatic adenocarcinoma cells by enhancing IL-1β expression

Binding of the transcription factor Slug to the L1CAM promoter is essential for transforming growth factor-β1 (TGF-β)-induced L1CAM expression in human pancreatic ductal adenocarcinoma cells

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