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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene

Authors: Yongwen Li, Hongbing Zhang, Hao Gong, Yin Yuan, Ying Li, Cong Wang, Weiting Li, Zihe Zhang, Minghui Liu, Hongyu Liu, Jun Chen

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood.

Methods

The expression level of CTTN in human non-small cell lung cancer (NSCLC) tissues was detected by qRT-PCR. Cell migration, invasion and invadopodia formation were assessed in vitro by wound-healing, transwell assay and immunofluorescence, respectively. The dual-luciferase reporter assay was used to identify the direct target of miR-182.

Results

Hepatocyte growth factor (HGF) and phorbol 12,13-dibutyrate (PDBu) can induce CTTN expression, motility, and invasion ability, as well as invadopodia formation in non-small cell lung cancer (NSCLC). Moreover, miR-182 suppressed metastasis and invadopodia formation by targeting CTTN in NSCLC. Our qRT-PCR results showed that CTTN expression was inversely correlated with miR-182 expression that suppressed invadopodia formation via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulated invadopodia function, and suppressed extracellular matrix(ECM) degradation in lung cancer cells by inhibiting cortactin.

Conclusion

Collectively, our results demonstrated that miR-182 targeted CTTN gene in NSCLC and suppressed lung cancer invadopodia formation, and thus suppressed lung cancer metastasis. This suggests a therapeutic application of miR-182 in NSCLC.
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Metadata
Title
miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene
Authors
Yongwen Li
Hongbing Zhang
Hao Gong
Yin Yuan
Ying Li
Cong Wang
Weiting Li
Zihe Zhang
Minghui Liu
Hongyu Liu
Jun Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0824-1

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