MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia
Abstract Background Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in...
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.5079 |
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| author | Yue Zhao Xiufeng Xie Lusong Tian Fang Liu Yulin Sun Haizhen Lu Xiaohang Zhao Yousheng Mao |
| author_facet | Yue Zhao Xiufeng Xie Lusong Tian Fang Liu Yulin Sun Haizhen Lu Xiaohang Zhao Yousheng Mao |
| author_sort | Yue Zhao |
| collection | DOAJ |
| description | Abstract Background Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. Methods CCK8, Transwell and wound‐healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. Results Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F‐actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. Conclusion MARCKSL1 promotes cell migration and invasion by interacting with F‐actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis. |
| format | Article |
| id | doaj-art-b076d27138c8419a8043574f374b25c4 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-b076d27138c8419a8043574f374b25c42024-11-25T07:56:32ZengWileyCancer Medicine2045-76342023-02-011233299331210.1002/cam4.5079MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodiaYue Zhao0Xiufeng Xie1Lusong Tian2Fang Liu3Yulin Sun4Haizhen Lu5Xiaohang Zhao6Yousheng Mao7Department of Thoracic Surgery China‐Japan Friendship Hospital Beijing ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaState Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract Background Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. Methods CCK8, Transwell and wound‐healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. Results Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F‐actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. Conclusion MARCKSL1 promotes cell migration and invasion by interacting with F‐actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.https://doi.org/10.1002/cam4.5079esophageal cancerinvadopodia formationMARCKSL1metastasis |
| spellingShingle | Yue Zhao Xiufeng Xie Lusong Tian Fang Liu Yulin Sun Haizhen Lu Xiaohang Zhao Yousheng Mao MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia Cancer Medicine esophageal cancer invadopodia formation MARCKSL1 metastasis |
| title | MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| title_full | MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| title_fullStr | MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| title_full_unstemmed | MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| title_short | MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| title_sort | marcksl1 interacted with f actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia |
| topic | esophageal cancer invadopodia formation MARCKSL1 metastasis |
| url | https://doi.org/10.1002/cam4.5079 |
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