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CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48

Oncogene volume 25, pages 2264–2272 (2006)Cite this article

Abstract

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have suggested that CDX2 is a tumor suppressor. However, CDX2 has not been reported to affect xenograft growth. Furthermore, CDX2 is rarely mutated in colon cancer, which has led to suggestions that it may play only a minor role as a tumor suppressor in colon cancer. To understand the functional contributions of CDX2 to colon cancer, we disrupted CDX2 in LOVO and SW48 human colon cancer cell lines by targeted homologous recombination. Consistent with the literature, disruption of CDX2 enhanced anchorage-dependent cell proliferation. However, homozygous loss of CDX2 led to significant inhibition of anchorage-independent growth in LOVO cells, and cell lethality in SW48 cells. Further analyses revealed that disruption of CDX2 led to anchorage-independent G1 to S growth arrest and anoikis. In vivo xenograft studies confirmed that disruption of CDX2 inhibited LOVO tumor growth. These data demonstrate that CDX2 mediates anchorage-independent growth and survival. Thus, CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.

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Acknowledgements

We are grateful to Vincent Yang for helpful suggestions on the manuscript. We thank the University of Michigan Comprehensive Cancer Center flow cytometry, tissue core, and sequencing facilities for assistance with FACS analyses, immunohistochemistry, and sequencing. This work was supported by NIH Grant K08DK59970, American Gastroenterological Association Research Scholar Award, and Glaxo Institute for Digestive Health Basic Research Award (DTD).

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA

    L H Dang, F Chen, C Ying, S Y Chun & S A Knock

  2. Department of Pathology, Division of Anatomic Pathology, University of Michigan, Ann Arbor, MI, USA

    H D Appelman

  3. Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA

    D T Dang

  4. The University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    L H Dang, H D Appelman & D T Dang

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  1. L H Dang
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Correspondence to D T Dang.

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Dang, L., Chen, F., Ying, C. et al. CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48. Oncogene 25, 2264–2272 (2006). https://doi.org/10.1038/sj.onc.1209247

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