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

1 Citation (Scopus)

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

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Colorectal Neoplasms
Neoplasm Metastasis
Catenins
Phosphatidylinositol 3-Kinases
DC-specific ICAM-3 grabbing nonintegrin
Matrix Metalloproteinases
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Neoplasms
Epithelial Cells
Cell Line
Survival

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yuan, Menglang ; Zhang, Xinsheng ; Zhang, Jingbo ; Wang, Keyong ; Zhang, Yu ; Shang, Wei ; Zhang, Yinan ; Cui, Jingyi ; Shi, Xiaomeng ; Na, Heya ; Fang, Deyu ; Zuo, Yunfei ; Ren, Shuangyi. / DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis. In: Cell Death and Differentiation. 2020 ; Vol. 27, No. 1. pp. 379-395.
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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.",
author = "Menglang Yuan and Xinsheng Zhang and Jingbo Zhang and Keyong Wang and Yu Zhang and Wei Shang and Yinan Zhang and Jingyi Cui and Xiaomeng Shi and Heya Na and Deyu Fang and Yunfei Zuo and Shuangyi Ren",
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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, vol. 27, no. 1, pp. 379-395. https://doi.org/10.1038/s41418-019-0361-2

DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis. / Yuan, Menglang; Zhang, Xinsheng; Zhang, Jingbo; Wang, Keyong; Zhang, Yu; Shang, Wei; Zhang, Yinan; Cui, Jingyi; Shi, Xiaomeng; Na, Heya; Fang, Deyu; Zuo, Yunfei; Ren, Shuangyi.

In: Cell Death and Differentiation, Vol. 27, No. 1, 01.01.2020, p. 379-395.

Research output: Contribution to journalArticle

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T1 - DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

AU - Yuan, Menglang

AU - Zhang, Xinsheng

AU - Zhang, Jingbo

AU - Wang, Keyong

AU - Zhang, Yu

AU - Shang, Wei

AU - Zhang, Yinan

AU - Cui, Jingyi

AU - Shi, Xiaomeng

AU - Na, Heya

AU - Fang, Deyu

AU - Zuo, Yunfei

AU - Ren, Shuangyi

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

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