Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway

Yeong Su Jang, Ju Hee Kang, Jong Kyu Woo, Hwan Mook Kim, Jong Ik Hwang, Sang Jin Lee, Ho Young Lee, Seung Hyun Oh

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell surface molecule that can mediate homophilic adhesion and promote neurite outgrowth from cultured dorsal root ganglion (DRG) neurons. Interestingly, Ninj1 overexpressed in human cancer; however, its role in metastasis is not clear. This study showed that inhibition of Ninj1 promotes lung cancer metastasis through interleukin 6 (IL-6)/STAT3 signaling. Ninj1 levels were relatively low in highly motile lung cancer cells. While inhibition of Ninj1 enhanced cell migration in lung cancer cells, overexpression of Ninj1 significantly suppressed it. We found that inhibition of Ninj1 significantly increased expression and secretion of IL-6 in A549 cells. We also found that inhibition of IL-6 decreased intercellular adhesion molecule 1 (ICAM-1) expression. In addition, inhibition of Ninj1 significantly increased cell motility and invasiveness of lung cancer cells. In an in vivo model, we found that Ninj1 suppression did not affect tumor growth but induced significant increase in incidence of lung metastasis, and sizes and number of tumor nodules. Taken together, our data clearly demonstrate that Ninj1 suppresses migration, invasion and metastasis of lung cancer via inhibition of the IL-6 signaling pathway in vitro and in vivo.

Original languageEnglish
Pages (from-to)383-395
Number of pages13
JournalInternational Journal of Cancer
Issue number2
Publication statusPublished - 2016 Jul 15

Bibliographical note

Funding Information:
Grant sponsor: Global Core Research Center (GCRC); Grant number: 2011-0030678; Grant sponsor: NRF, MEST, Republic of Korea

Publisher Copyright:
© 2016 UICC.


  • intercellular adhesion molecule 1
  • interleukin 6
  • lung cancer
  • metastasis
  • nerve injury-induced protein 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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