Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalCancer Gene Therapy
Publication statusAccepted/In press - 2022

Bibliographical note

Funding Information:
This work was supported by the Korean Gastroenterology Fund for Future Development and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2020R1A2C1005322). We would like to thank the donors for their contribution to this study.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research


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