<i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i>
Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. <i>LLGL2</i>, as a cell polarity factor, is in...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/24/5880 |
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| author | Qiu-Ying Gu Yue-Xi Liu Jin-Long Wang Xiao-Lan Huang Ruo-Nan Li Hua Linghu |
| author_facet | Qiu-Ying Gu Yue-Xi Liu Jin-Long Wang Xiao-Lan Huang Ruo-Nan Li Hua Linghu |
| author_sort | Qiu-Ying Gu |
| collection | DOAJ |
| description | Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. <i>LLGL2</i>, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, <i>LLGL2</i> regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of <i>LLGL2</i> in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of <i>LLGL2</i> was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved <i>LLGL2</i> overexpression and knockdown showed that <i>LLGL2</i> inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells. |
| first_indexed | 2024-03-08T20:55:11Z |
| format | Article |
| id | doaj.art-e781f947203849f2894f06a7250d68b5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T20:55:11Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e781f947203849f2894f06a7250d68b52023-12-22T13:59:09ZengMDPI AGCancers2072-66942023-12-011524588010.3390/cancers15245880<i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i>Qiu-Ying Gu0Yue-Xi Liu1Jin-Long Wang2Xiao-Lan Huang3Ruo-Nan Li4Hua Linghu5Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaEpithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. <i>LLGL2</i>, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, <i>LLGL2</i> regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of <i>LLGL2</i> in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of <i>LLGL2</i> was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved <i>LLGL2</i> overexpression and knockdown showed that <i>LLGL2</i> inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells.https://www.mdpi.com/2072-6694/15/24/5880<i>LLGL2</i>ovarian cancertumor metastasisF-actin<i>ACTN1</i> |
| spellingShingle | Qiu-Ying Gu Yue-Xi Liu Jin-Long Wang Xiao-Lan Huang Ruo-Nan Li Hua Linghu <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> Cancers <i>LLGL2</i> ovarian cancer tumor metastasis F-actin <i>ACTN1</i> |
| title | <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> |
| title_full | <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> |
| title_fullStr | <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> |
| title_full_unstemmed | <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> |
| title_short | <i>LLGL2</i> Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via <i>ACTN1</i> |
| title_sort | i llgl2 i inhibits ovarian cancer metastasis by regulating cytoskeleton remodeling via i actn1 i |
| topic | <i>LLGL2</i> ovarian cancer tumor metastasis F-actin <i>ACTN1</i> |
| url | https://www.mdpi.com/2072-6694/15/24/5880 |
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