Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer

被引：2

作者：

Ma, Hyun Woo ^{[1
,2
]}

Kim, Jung Min ^{[3
,4
]}

Kim, Da Hye ^{[3
,4
]}

Park, I. Seul ^{[1
,2
]}

Kim, Ji Hyung ^{[1
,2
]}

Park, Ki Cheong ^{[5
]}

Seo, Dong Hyuk ^{[1
,2
]}

Kim, Jae Hyeon ^{[1
,2
]}

Che, Xiumei ^{[1
,2
]}

Kim, Tae Il ^{[1
,2
]}

Cheon, Jae Hee ^{[1
,2
,6
]}

Kim, Seung Won ^{[1
,2
,6
]}

机构：

[1] Yonsei Univ, Grad Sch Med Sci, Dept Internal Med, Coll Med,Brain Korea Project 21, Seoul, South Korea

[2] Yonsei Univ, Inst Gastroenterol, Grad Sch Med Sci, Coll Med,Brain Korea Project 21, Seoul, South Korea

[3] Yonsei Univ, Dept Internal Med, Coll Med, Seoul, South Korea

[4] Yonsei Univ, Inst Gastroenterol, Coll Med, Seoul, South Korea

[5] Yonsei Univ, Dept Surg, Coll Med, Seoul, South Korea

[6] Yonsei Univ, Severance Biomed Sci Inst, Coll Med, Seoul, South Korea

来源：

CANCER GENE THERAPY | 2023年 / 30卷 / 05期

基金：

新加坡国家研究基金会;

关键词：

TGF-BETA; INNATE IMMUNITY; UP-REGULATION; INFLAMMATION; EXPRESSION; GENE; CELLS; PROGRESSION; DELETION; GW112;

D O I：

10.1038/s41417-022-00585-9

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：694 / 703

页数：10