Annals of Surgical Oncology

, Volume 18, Issue 4, pp 1166–1174 | Cite as

Significance of Lgr5+ve Cancer Stem Cells in the Colon and Rectum

  • Hidekazu Takahashi
  • Hideshi Ishii
  • Naohiro Nishida
  • Ichiro Takemasa
  • Tsunekazu Mizushima
  • Masataka Ikeda
  • Takehiko Yokobori
  • Koshi Mimori
  • Hirofumi Yamamoto
  • Mitsugu Sekimoto
  • Yuichiro Doki
  • Masaki Mori
Translational Research and Biomarkers



Although recent studies show that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)+ve cells targeted by Wnt drive self-renewal in the skin and gastrointestinal organs, the clinicopathological significance of Lgr5+ve cancer stem cells (CSCs) of the colon remains to be elucidated.

Experimental Design

We studied the Wnt-targeted Lgr5 pathway in colorectal cancer (CRC). The expression of LGR5, c-MYC, p21CIP1/WAF1/CDKN1A, glutaminase (GLS), and miRs-23a and -23b (that target LGR5 and GLS) was evaluated by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). The Lgr5 protein was evaluated by immunohistochemistry. The clinical relevance of gene expression in terms of patient survival was also evaluated.


Overexpression of LGR5 was significantly associated with expression of c-MYC, p21CIP1/WAF1/CDKN1A, and GLS (p < 0.0001), and inversely associated with miR-23a/b (p < 0.05). Immunohistochemical analysis indicated that Lgr5 may be embedded in benign adenomas, localized at the tumor–host interface, and detectable over a broad area in established tumors. High level of LGR5 expression was associated with poor prognosis for CRC cancer patients (disease-free survival; p < 0.05).


This study supports a significant role for LGR5 in the CSC hypothesis in CRC: (1) Lgr5+ve CSCs, presumably derived from normal stem cells in colonic crypts, proliferate, and the gene is overexpressed during CRC development; (2) LGR5 expression is associated with activation of Wnt pathway, including oncogenic c-MYC and high energy production via glutaminolysis; (3) LGR5 expression may be a poor prognostic factor for CRC patients. Further study of LGR5 should contribute to the development of CSC-based cancer therapeutics.


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Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Hidekazu Takahashi
    • 1
  • Hideshi Ishii
    • 1
    • 2
  • Naohiro Nishida
    • 1
    • 2
  • Ichiro Takemasa
    • 1
  • Tsunekazu Mizushima
    • 1
  • Masataka Ikeda
    • 1
    • 2
  • Takehiko Yokobori
    • 2
  • Koshi Mimori
    • 2
  • Hirofumi Yamamoto
    • 1
  • Mitsugu Sekimoto
    • 1
  • Yuichiro Doki
    • 1
  • Masaki Mori
    • 1
    • 2
  1. 1.Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
  2. 2.Department of Molecular and Cellular Biology, Division of Molecular and Surgical OncologyKyushu University, Medical Institute of BioregulationOhitaJapan

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