Description:
<jats:title>Abstract</jats:title>
<jats:p>Metastasis is the major cause of death for patients with solid tumors, mainly due to the lack of effective therapies once metastases begin to form. Further research into the mechanism of metastasis is therefore essential in order to have a better understanding of this process and eventually develop more efficient cancer therapies to prevent or treat metastasis. LGR5 is a leucin-rich G protein coupled receptor and a Wnt target gene. It marks the proliferating adult stem cells in the small intestine and has been shown to play an important role in the maintenance of intestine stem cell proliferation by enhancing the canonical Wnt signaling. It is overexpressed in human colorectal, ovary and liver tumors due to the inappropriate activation of Wnt signaling at the onset of those diseases. Recent studies are conflicting regarding the functional role of LGR5 in colon cancer initiation. However, its role in colon cancer progression and metastasis has not been studied. Analysis of copy number variation (CNV) of LGR5 from the Cancer Genome Atlas (TCGA) database revealed that CNV loss of LGR5 is enriched in late stage colon cancer (stage III and IV) with high lymph node spread and/or distant metastasis and in patients with recurrence whereas CNV gain is enriched in early stage disease with no regional or distant metastasis. These results suggest that LGR5 expression may increase during the onset of colon tumorigenesis and decrease thereafter during tumor progression. Functional studies showed that knockdown of LGR5 expression in colon cancer cells increased their clonogenecity, survival capacity and motility in vitro and metastatic dissemination to the liver and lungs in an orthotopic model in vivo. Our results demonstrate that LGR5 functions as a suppressor of colon cancer metastasis and that reduction of LGR5 expression contributes to colon cancer progression and metastasis.</jats:p>
<jats:p>Citation Format: Xiaolin Zhou, Jing Jenny Wang. LGR5 suppresses colon cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3252. doi:10.1158/1538-7445.AM2015-3252</jats:p>