KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway
Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role i...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.679173/full |
| _version_ | 1818718894418821120 |
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| author | Lin Gao Ru Zhao Junmei Liu Wenbo Zhang Feifei Sun Qianshuo Yin Xin Wang Meng Wang Tingting Feng Yiming Qin Wenjie Cai Qianni Li Hanchen Dong Xueqing Chen Xueting Xiong Hui Liu Hui Liu Jing Hu Jing Hu Weiwen Chen Bo Han Bo Han |
| author_facet | Lin Gao Ru Zhao Junmei Liu Wenbo Zhang Feifei Sun Qianshuo Yin Xin Wang Meng Wang Tingting Feng Yiming Qin Wenjie Cai Qianni Li Hanchen Dong Xueqing Chen Xueting Xiong Hui Liu Hui Liu Jing Hu Jing Hu Weiwen Chen Bo Han Bo Han |
| author_sort | Lin Gao |
| collection | DOAJ |
| description | Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target. |
| first_indexed | 2024-12-17T19:58:18Z |
| format | Article |
| id | doaj.art-1b1019cfeb5f457cab5f3e84145a13bb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T19:58:18Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1b1019cfeb5f457cab5f3e84145a13bb2022-12-21T21:34:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.679173679173KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling PathwayLin Gao0Ru Zhao1Junmei Liu2Wenbo Zhang3Feifei Sun4Qianshuo Yin5Xin Wang6Meng Wang7Tingting Feng8Yiming Qin9Wenjie Cai10Qianni Li11Hanchen Dong12Xueqing Chen13Xueting Xiong14Hui Liu15Hui Liu16Jing Hu17Jing Hu18Weiwen Chen19Bo Han20Bo Han21The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Basic Medical Sciences, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaCollege of Chemical Engineering and Materials Science, Shandong Normal University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaCastration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.https://www.frontiersin.org/articles/10.3389/fonc.2021.679173/fullKIF15EGFRCdc42CRPCprotein stability |
| spellingShingle | Lin Gao Ru Zhao Junmei Liu Wenbo Zhang Feifei Sun Qianshuo Yin Xin Wang Meng Wang Tingting Feng Yiming Qin Wenjie Cai Qianni Li Hanchen Dong Xueqing Chen Xueting Xiong Hui Liu Hui Liu Jing Hu Jing Hu Weiwen Chen Bo Han Bo Han KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway Frontiers in Oncology KIF15 EGFR Cdc42 CRPC protein stability |
| title | KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway |
| title_full | KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway |
| title_fullStr | KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway |
| title_full_unstemmed | KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway |
| title_short | KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway |
| title_sort | kif15 promotes progression of castration resistant prostate cancer by activating egfr signaling pathway |
| topic | KIF15 EGFR Cdc42 CRPC protein stability |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.679173/full |
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