Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma
Epithelial–mesenchymal transition (EMT) is associated with malignant tumors. In a previous study, we found that KLHL23 is a tumor suppressor gene that inhibits EMT and cancer dissemination. However, the correlation between its expression and cancer progression in urothelial carcinoma (UC) remains un...
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| Format: | Article |
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Wolters Kluwer Medknow Publications
2021-01-01
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| Series: | Chinese Journal of Physiology |
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| Online Access: | http://www.cjphysiology.org/article.asp?issn=0304-4920;year=2021;volume=64;issue=3;spage=142;epage=149;aulast=Peng |
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| author | Jei-Ming Peng Sen-Yung Hsieh Jai-Hong Cheng Jia-Wun Luo Yu-Li Su Hao-Lun Luo |
| author_facet | Jei-Ming Peng Sen-Yung Hsieh Jai-Hong Cheng Jia-Wun Luo Yu-Li Su Hao-Lun Luo |
| author_sort | Jei-Ming Peng |
| collection | DOAJ |
| description | Epithelial–mesenchymal transition (EMT) is associated with malignant tumors. In a previous study, we found that KLHL23 is a tumor suppressor gene that inhibits EMT and cancer dissemination. However, the correlation between its expression and cancer progression in urothelial carcinoma (UC) remains unknown. This study showed that the deficiency of KLHL23 in the invasive leading cancer cells is important for improving cell migration in UC. Currently, little is known about the underlying mechanisms of KLHL23-mediated cytoskeleton remodeling in the metastatic leading cells of tumors. Our findings showed that silencing of KLHL23 promotes cell migration in UC by regulating the translocation of focal adhesion proteins. Lack of KLHL23 causes abnormal formation of lamellipodia and increases the EMT phenotype and migration. Wound healing assay revealed that KLHL23 potentiates the actin bundles and intracellular focal adhesion protein formation in the invasive leading cells. Knockdown of KLHL23 abolishes the formation of actin stress fibers and translocalizes vinculin to the perimembrane, which enhances the mobility of cancer cells. To elucidate the mechanism, we found that during migration, KLHL23 appears in the leading cells in large numbers and binds to the actin stress fibers. A large amount of vinculin accumulated at both ends of the KLHL23/actin fibers, indicating an increase in cell anchorage. Thus, KLHL23 might play a critical role in enhancing actin fibers and promoting focal adhesion complex formation in the invasive leading cells. Analysis of the overall survival revealed that low KLHL23 is associated with poor survival in patients with bladder UC, indicating its clinical significance. We hypothesize that KLHL23 is involved in the formation of actin stress fibers and focal adhesion complexes in the invasive leading cells and may be associated with EMT progression and prognosis in UC patients. |
| first_indexed | 2024-12-17T21:13:52Z |
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| id | doaj.art-40585df579664e339593de8c254dfff0 |
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| issn | 0304-4920 2666-0059 |
| language | English |
| last_indexed | 2024-12-17T21:13:52Z |
| publishDate | 2021-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Chinese Journal of Physiology |
| spelling | doaj.art-40585df579664e339593de8c254dfff02022-12-21T21:32:23ZengWolters Kluwer Medknow PublicationsChinese Journal of Physiology0304-49202666-00592021-01-0164314214910.4103/cjp.cjp_110_20Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinomaJei-Ming PengSen-Yung HsiehJai-Hong ChengJia-Wun LuoYu-Li SuHao-Lun LuoEpithelial–mesenchymal transition (EMT) is associated with malignant tumors. In a previous study, we found that KLHL23 is a tumor suppressor gene that inhibits EMT and cancer dissemination. However, the correlation between its expression and cancer progression in urothelial carcinoma (UC) remains unknown. This study showed that the deficiency of KLHL23 in the invasive leading cancer cells is important for improving cell migration in UC. Currently, little is known about the underlying mechanisms of KLHL23-mediated cytoskeleton remodeling in the metastatic leading cells of tumors. Our findings showed that silencing of KLHL23 promotes cell migration in UC by regulating the translocation of focal adhesion proteins. Lack of KLHL23 causes abnormal formation of lamellipodia and increases the EMT phenotype and migration. Wound healing assay revealed that KLHL23 potentiates the actin bundles and intracellular focal adhesion protein formation in the invasive leading cells. Knockdown of KLHL23 abolishes the formation of actin stress fibers and translocalizes vinculin to the perimembrane, which enhances the mobility of cancer cells. To elucidate the mechanism, we found that during migration, KLHL23 appears in the leading cells in large numbers and binds to the actin stress fibers. A large amount of vinculin accumulated at both ends of the KLHL23/actin fibers, indicating an increase in cell anchorage. Thus, KLHL23 might play a critical role in enhancing actin fibers and promoting focal adhesion complex formation in the invasive leading cells. Analysis of the overall survival revealed that low KLHL23 is associated with poor survival in patients with bladder UC, indicating its clinical significance. We hypothesize that KLHL23 is involved in the formation of actin stress fibers and focal adhesion complexes in the invasive leading cells and may be associated with EMT progression and prognosis in UC patients.http://www.cjphysiology.org/article.asp?issn=0304-4920;year=2021;volume=64;issue=3;spage=142;epage=149;aulast=Pengactin cytoskeleton remodelingbladder urothelial carcinomafocal adhesionmigrationtumor suppressor gene |
| spellingShingle | Jei-Ming Peng Sen-Yung Hsieh Jai-Hong Cheng Jia-Wun Luo Yu-Li Su Hao-Lun Luo Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma Chinese Journal of Physiology actin cytoskeleton remodeling bladder urothelial carcinoma focal adhesion migration tumor suppressor gene |
| title | Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma |
| title_full | Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma |
| title_fullStr | Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma |
| title_full_unstemmed | Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma |
| title_short | Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma |
| title_sort | confirming whether klhl23 deficiency potentiates migration in urothelial carcinoma |
| topic | actin cytoskeleton remodeling bladder urothelial carcinoma focal adhesion migration tumor suppressor gene |
| url | http://www.cjphysiology.org/article.asp?issn=0304-4920;year=2021;volume=64;issue=3;spage=142;epage=149;aulast=Peng |
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