PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells
Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304221000325 |
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| author | Zhili Wei Ru Wang Xun Yin lian Zhang Yunlong Lei Ying Zhang Yi Li Jiaqian Wu Youquan Bu Guoxiang Jin Chundong Zhang |
| author_facet | Zhili Wei Ru Wang Xun Yin lian Zhang Yunlong Lei Ying Zhang Yi Li Jiaqian Wu Youquan Bu Guoxiang Jin Chundong Zhang |
| author_sort | Zhili Wei |
| collection | DOAJ |
| description | Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185–200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAKY397) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting ARP2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells. |
| first_indexed | 2024-03-12T09:08:19Z |
| format | Article |
| id | doaj.art-c80b914e53ab47a4951686b400c19664 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T09:08:19Z |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-c80b914e53ab47a4951686b400c196642023-09-02T15:13:18ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-01-0191230244PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cellsZhili Wei0Ru Wang1Xun Yin2lian Zhang3Yunlong Lei4Ying Zhang5Yi Li6Jiaqian Wu7Youquan Bu8Guoxiang Jin9Chundong Zhang10Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR China; Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR ChinaDepartment of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, PR China; Corresponding author. Department of Biochemistry and Molecular Biology, Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China.Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185–200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAKY397) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting ARP2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.http://www.sciencedirect.com/science/article/pii/S2352304221000325ARP2/3 complexCell motilityFAKFilopodiaFocal adhesionIntegrin |
| spellingShingle | Zhili Wei Ru Wang Xun Yin lian Zhang Yunlong Lei Ying Zhang Yi Li Jiaqian Wu Youquan Bu Guoxiang Jin Chundong Zhang PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells Genes and Diseases ARP2/3 complex Cell motility FAK Filopodia Focal adhesion Integrin |
| title | PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells |
| title_full | PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells |
| title_fullStr | PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells |
| title_full_unstemmed | PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells |
| title_short | PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells |
| title_sort | prr11 induces filopodia formation and promotes cell motility via recruiting arp2 3 complex in non small cell lung cancer cells |
| topic | ARP2/3 complex Cell motility FAK Filopodia Focal adhesion Integrin |
| url | http://www.sciencedirect.com/science/article/pii/S2352304221000325 |
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