Positive feedback regulation between IL10 and EGFR promotes lung cancer formation

Tsung I. Hsu, Yi Chang Wang, Chia Yang Hung, Chun Hui Yu, Wu Chou Su, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The role of IL10 in the tumorigenesis of various cancer types is still controversial. Here, we found that increased IL10 levels are correlated with a poor prognosis in lung cancer patients. Moreover, IL10 levels were significantly increased in the lungs and serum of EGFRL858R- and Kras4bG12D-induced lung cancer mice, indicating that IL10 might facilitate lung cancer tumorigenesis. IL10 knockout in EGFRL858R and Kras4bG12D mice inhibited the development of lung tumors and decreased the levels of infiltrating M2 macrophages and tumor-promoting Treg lymphocytes. We also showed that EGF increases IL10 expression by enhancing IL10 mRNA stability, and IL10 subsequently activates JAK1/STAT3, Src, PI3K/Akt, and Erk signaling pathways. Interestingly, the IL10-induced recruitment of phosphorylated Src was critical for inducing EGFR through the activation of the JAK1/STAT3 pathway, suggesting that Src and JAK1 positively regulate each other to enhance STAT3 activity. Doxycycline-induced EGFRL858R mice treated with gefitinib and anti-IL10 antibodies exhibited poor tumor formation. In conclusion, IL10 and EGFR regulate each other through positive feedback, which leads to lung cancer formation.

Original languageEnglish
Pages (from-to)20840-20854
Number of pages15
JournalOncotarget
Volume7
Issue number15
DOIs
Publication statusPublished - Apr 12 2016

Keywords

  • EGFR
  • IL10
  • Nucleolin
  • Src

ASJC Scopus subject areas

  • Oncology

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