1. ¹Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA
2. ²Department of Pathology, Division of Anatomic Pathology, University of Michigan, Ann Arbor, MI, USA
3. ³Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
4. ⁴The University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

Correspondence: Dr DT Dang, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, 1150 W. Medical Center Drive, MSRB I, Room 6514, Ann Arbor, MI 48109-0682, USA. E-mail: dangd@umich.edu

Received 13 September 2005; Revised 6 October 2005; Accepted 6 October 2005; Published online 28 November 2005.

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.