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Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma
Jei-Ming Peng1, Sen-Yung Hsieh2, Jai-Hong Cheng3, Jia-Wun Luo1, Yu-Li Su4, Hao-Lun Luo5
1 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital; Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
3 Center for Shockwave Medicine and Tissue Engineering, Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine; Department of Leisure and Sports Management, Cheng Shiu University, Kaohsiung, Taiwan
4 Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
5 Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Correspondence Address:
Dr. Hao-Lun Luo
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833
Taiwan
Dr. Jei-Ming Peng
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833
Taiwan
Dr. Yu-Li Su
Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/cjp.cjp_110_20
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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.
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