DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

Menglang Yuan, Xinsheng Zhang, Jingbo Zhang, Keyong Wang, Yu Zhang, Wei Shang, Yinan Zhang, Jingyi Cui, Xiaomeng Shi, Heya Na, Deyu Fang, Yunfei Zuo, Shuangyi Ren*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

DC-SIGN is previously focused on its physiologic and pathophysiologic roles in immune cells. Little is known about whether DC-SIGN is expressed in malignant epithelial cells and how DC-SIGN participates in tumor progression. Here we showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. Gain of DC-SIGN function facilitated the CRC metastases both in vitro and in vivo, and this effect was reversed by miR-185. DC-SIGN and Lyn interacted physically, and Lyn maintained the stability of DC-SIGN in cells. DC-SIGN activation recruited Lyn and p85 to form the DC-SIGN-Lyn-p85 complex, which promoted CRC metastasis by increasing PI3K/Akt/β-catenin signaling in tyrosine kinase Lyn-dependent manner. Furthermore, activation of DC-SIGN promoted the transcription of MMP-9 and VEGF by increasing PI3K/Akt/β-catenin signaling, and induced TCF1/LEF1-mediated suppression of miR-185. Our findings reveal the presence of the DC-SIGN–TCF1/LEF1–miR-185 loop in cancer cells with metastatic traits, implying that it may represent a new pathogenic mechanism of CRC metastasis. This character of the loop promises to provide new targets for blocking CRC invasive and metastatic activity.

Original languageEnglish (US)
Pages (from-to)379-395
Number of pages17
JournalCell Death and Differentiation
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Yuan, M., Zhang, X., Zhang, J., Wang, K., Zhang, Y., Shang, W., Zhang, Y., Cui, J., Shi, X., Na, H., Fang, D., Zuo, Y., & Ren, S. (2020). DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis. Cell Death and Differentiation, 27(1), 379-395. https://doi.org/10.1038/s41418-019-0361-2