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Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer

Authors
 Hyun Woo Ma  ;  Jung Min Kim  ;  Da Hye Kim  ;  I Seul Park  ;  Ji Hyung Kim  ;  Ki Cheong Park  ;  Dong Hyuk Seo  ;  Jae Hyeon Kim  ;  Xiumei Che  ;  Tae Il Kim  ;  Jae Hee Cheon  ;  Seung Won Kim 
Citation
 CANCER GENE THERAPY, Vol.30(5) : 694-703, 2023-05 
Journal Title
CANCER GENE THERAPY
ISSN
 0929-1903 
Issue Date
2023-05
Abstract
Development of colorectal cancer (CRC) is regulated by a series of genetic and microenvironmental alterations. Olfactomedin 4 (OLFM4) is a secreted glycoprotein that is highly expressed in the gastrointestinal tract and modulates inflammation. However, the role of OLFM4 in CRC is uncertain. Here we aimed to explore the function of OLFM4 in CRC in vivo and in vitro. The mRNA expression of OLFM4 was up-regulated in precursor lesions with dysplasia or ulcerative colitis but was reduced in CRC. OLFM4 neutralizing antibody suppressed inflammation-mediated early-stage CRC formation in an AOM/DSS colitis-associated cancer model. OLFM4 knockdown cells exhibited increased cell proliferation and motility in vitro and in vivo. Ablation of OLFM4 increased tumor growth and metastasis in xenograft experiments. In addition, OLFM4 knockdown cells showed elevated expression of colon cancer stem cell markers including CD133, resulting in increased metastasis via epithelial-mesenchymal transition signaling. This study demonstrated that OLFM4 regulates inflammation and cancer progression differently; ablation of OLFM4 promotes cancer metastasis via stemness and epithelial-mesenchymal transition. These results suggest a new route for controlling cancer progression and metastasis.
Full Text
https://www.nature.com/articles/s41417-022-00585-9
DOI
10.1038/s41417-022-00585-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193923
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