Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain

Stange, Daniel E.; Engel, Felix B.; Longerich, Thomas; Koo, Bon–Kyoung; Koch, Moritz; Delhomme, Nicolas; Aigner, Maximilian; Toedt, Grischa; Schirmacher, Peter; Lichter, Peter; Weitz, Jürgen; Radlwimmer, Bernhard

doi:10.1136/gut.2009.195701

Cited by 91 publications

(94 citation statements)

References 52 publications

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“…In 70 samples, PKLR mRNA was significantly upregulated in liver metastases relative to primary tumors ( Figure 3A). This upregulation was also observed in multiple independent data sets of unmatched ( Figure 3, B and C) and matched ( Figure 3, D and E) samples from patients with colorectal cancer (24)(25)(26)(27). These samples were from a total of 311 patients.…”

Section: Resultsmentioning

confidence: 74%

PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

Nguyen¹,

Loo²,

Mital³

et al. 2016

Journal of Clinical Investigation

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Section: Resultsmentioning

confidence: 74%

PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

Nguyen¹,

Loo²,

Mital³

et al. 2016

Journal of Clinical Investigation

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“…Most distant metastases genotypically and phenotypically resemble their primary tumor (11). This implicates that the changes enabling CTC to perform the necessary steps to cause distant metastases must be reversible and, thus, on a transcriptomic rather than a genomic level.…”

Section: Discussionmentioning

confidence: 99%

“…The dramatic phenotypic changes tumor cells need to undergo to become functional and tumorigenic CTC are no longer present in outgrown metastatic tumors and must therefore be reversible (9)(10)(11). This reversible phenotype is probably based on temporary differential regulation of metastasis-related genes.…”

Section: Introductionmentioning

confidence: 99%

Immune Escape and Survival Mechanisms in Circulating Tumor Cells of Colorectal Cancer

et al. 2014

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The prognosis of colorectal cancer is closely linked to the occurrence of distant metastases. Systemic dissemination is most likely caused by circulating tumor cells (CTC). Despite the fundamental role of CTC within the metastatic cascade, technical obstacles have so far prevented detailed genomic and, in particular, phenotypic analyses of CTC, which may provide molecular targets to delay or prevent distant metastases. We show here a detailed genomic analysis of single colorectal cancer-derived CTC by array comparative genomic hybridization (aCGH), mutational profiling, and microsatellite instability (MSI) analysis. Furthermore, we report the first gene expression analysis of manually selected colorectal cancer-derived CTC by quantitative real-time PCR (qRT-PCR) to investigate transcriptional changes, enabling CTC to survive in circulation and form distant metastases. aCGH confirmed the tumor cell identity of CellSearch-isolated colorectal cancer-derived CTC. Mutational and MSI analyses revealed mutational profiles of CTC to be similar, but not identical to the corresponding tumor tissue. Several CTC exhibited mutations in key genes such as KRAS or TP53 that could not be detected in the tumor. Gene expression analyses revealed both a pronounced upregulation of CD47 as a potential immune-escape mechanism and a significant downregulation of several other pathways, suggesting a dormant state of viable CTC. Our results suggest mutational heterogeneity between tumor tissue and CTC that should be considered in future trials on targeted therapy and monitoring of response. The finding of upregulated immune-escape pathways, which may be responsible for survival of CTC in circulation, could provide a promising target to disrupt the metastatic cascade in colorectal cancer. Cancer Res; 74(6); 1694-704. Ó2014 AACR.

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“…The combined results from such gain-and loss-of-function experiments indicate that Ascl2 controls the fate of intestinal stem cells (6). Several groups have demonstrated that Ascl2 is overexpressed in colorectal cancer (5,7,8). In addition, Ascl2 overexpression has the potential to shift the hierarchy of stem and progenitor cells within liver metastases, resulting in self-renewal rather than differentiation and potentially affecting the clinical behavior of these tumors (8).…”

mentioning

confidence: 99%

MicroRNA-200 (miR-200) Cluster Regulation by Achaete Scute-like 2 (Ascl2)

Yin

Pan

Shang

et al. 2014

Journal of Biological Chemistry

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Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain

Cited by 91 publications

References 52 publications

PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

Immune Escape and Survival Mechanisms in Circulating Tumor Cells of Colorectal Cancer

MicroRNA-200 (miR-200) Cluster Regulation by Achaete Scute-like 2 (Ascl2)

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