miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene
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. Co...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0824-1 |
| _version_ | 1818948862479433728 |
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| author | Yongwen Li Hongbing Zhang Hao Gong Yin Yuan Ying Li Cong Wang Weiting Li Zihe Zhang Minghui Liu Hongyu Liu Jun Chen |
| author_facet | Yongwen Li Hongbing Zhang Hao Gong Yin Yuan Ying Li Cong Wang Weiting Li Zihe Zhang Minghui Liu Hongyu Liu Jun Chen |
| author_sort | Yongwen Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T08:53:32Z |
| format | Article |
| id | doaj.art-beb8f3c5bd534f21b5753a8d48ece8b6 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-20T08:53:32Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-beb8f3c5bd534f21b5753a8d48ece8b62022-12-21T19:46:04ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-07-0137111510.1186/s13046-018-0824-1miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin geneYongwen Li0Hongbing Zhang1Hao Gong2Yin Yuan3Ying Li4Cong Wang5Weiting Li6Zihe Zhang7Minghui Liu8Hongyu Liu9Jun Chen10Tianjin key laboratory of lung cancer metastasis and tumor microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalTianjin key laboratory of lung cancer metastasis and tumor microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalTianjin key laboratory of lung cancer metastasis and tumor microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General HospitalDepartment of Lung Cancer Surgery, Tianjin Medical University General HospitalAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0824-1Lung cancermiRNA-182CortactinMetastasisInvadopodia |
| spellingShingle | Yongwen Li Hongbing Zhang Hao Gong Yin Yuan Ying Li Cong Wang Weiting Li Zihe Zhang Minghui Liu Hongyu Liu Jun Chen miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene Journal of Experimental & Clinical Cancer Research Lung cancer miRNA-182 Cortactin Metastasis Invadopodia |
| title | miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene |
| title_full | miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene |
| title_fullStr | miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene |
| title_full_unstemmed | miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene |
| title_short | miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene |
| title_sort | mir 182 suppresses invadopodia formation and metastasis in non small cell lung cancer by targeting cortactin gene |
| topic | Lung cancer miRNA-182 Cortactin Metastasis Invadopodia |
| url | http://link.springer.com/article/10.1186/s13046-018-0824-1 |
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