RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis
Abstract Enkurin, TRPC Channel Interacting Protein (ENKUR) was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, an...
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| Language: | English |
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Wiley
2022-12-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.185 |
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| author | Jiahao Liu Zhan Liu Weiwei Yan Huiling Yang Shiyi Fang Shuting Deng Yinghao Wen Peng Shen Yonghao Li Rentao Hou Xiong Liu Tao Huang Rong Li Dayong Zheng Zhen Liu Weiyi Fang |
| author_facet | Jiahao Liu Zhan Liu Weiwei Yan Huiling Yang Shiyi Fang Shuting Deng Yinghao Wen Peng Shen Yonghao Li Rentao Hou Xiong Liu Tao Huang Rong Li Dayong Zheng Zhen Liu Weiyi Fang |
| author_sort | Jiahao Liu |
| collection | DOAJ |
| description | Abstract Enkurin, TRPC Channel Interacting Protein (ENKUR) was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, and metastasis in GC. The molecular basis showed β‐catenin‐mediated epithelial‐mesenchymal transition (EMT) signaling was inactivated in ENKUR‐overexpressing GC cells. In addition, ENKUR knockdown markedly restored cell migration and invasion. Subsequently, ENKUR bound to MYH9 and decreased its protein expression by recruiting E3 ubiquitin ligase F‐Box And WD Repeat Domain Containing 7 (FBXW7) to form an ubiquitinated degradation complex. The downregulated Myosin Heavy Chain 9 (MYH9) protein weakened the recruitment of the deubiquitinase USP2 and thus promoted the degradation of β‐catenin protein, which finally suppressed EMT signaling. Finally, the oncogenic transcription factor c‐Jun bound to ENKUR promoter and reduced its expression in GC. In clinical samples, decreased ENKUR expression promoted the unfavorable prognosis of GC. Our data proved the vital role of ENKUR on suppressing cell migration, invasion, and metastasis and demonstrated its potential as a therapeutic target for GC. |
| format | Article |
| id | doaj-art-4c9a020c082a40b294c9a8881ab2ec6d |
| institution | OA Journals |
| issn | 2688-2663 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-4c9a020c082a40b294c9a8881ab2ec6d2025-08-20T02:04:31ZengWileyMedComm2688-26632022-12-0134n/an/a10.1002/mco2.185RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasisJiahao Liu0Zhan Liu1Weiwei Yan2Huiling Yang3Shiyi Fang4Shuting Deng5Yinghao Wen6Peng Shen7Yonghao Li8Rentao Hou9Xiong Liu10Tao Huang11Rong Li12Dayong Zheng13Zhen Liu14Weiyi Fang15Cancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaDepartment of Gastroenterology Hunan People's Hospital Changsha P.R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaSchool of Pharmacy Guangdong Medical University Dongguan P.R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaOncology Department Nanfang Hospital Southern Medical University Guangzhou P.R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaOncology Department Nanfang Hospital Southern Medical University Guangzhou P.R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou P. R. ChinaAbstract Enkurin, TRPC Channel Interacting Protein (ENKUR) was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, and metastasis in GC. The molecular basis showed β‐catenin‐mediated epithelial‐mesenchymal transition (EMT) signaling was inactivated in ENKUR‐overexpressing GC cells. In addition, ENKUR knockdown markedly restored cell migration and invasion. Subsequently, ENKUR bound to MYH9 and decreased its protein expression by recruiting E3 ubiquitin ligase F‐Box And WD Repeat Domain Containing 7 (FBXW7) to form an ubiquitinated degradation complex. The downregulated Myosin Heavy Chain 9 (MYH9) protein weakened the recruitment of the deubiquitinase USP2 and thus promoted the degradation of β‐catenin protein, which finally suppressed EMT signaling. Finally, the oncogenic transcription factor c‐Jun bound to ENKUR promoter and reduced its expression in GC. In clinical samples, decreased ENKUR expression promoted the unfavorable prognosis of GC. Our data proved the vital role of ENKUR on suppressing cell migration, invasion, and metastasis and demonstrated its potential as a therapeutic target for GC.https://doi.org/10.1002/mco2.185cell metastasisENKURgastric cancerMYH9 |
| spellingShingle | Jiahao Liu Zhan Liu Weiwei Yan Huiling Yang Shiyi Fang Shuting Deng Yinghao Wen Peng Shen Yonghao Li Rentao Hou Xiong Liu Tao Huang Rong Li Dayong Zheng Zhen Liu Weiyi Fang RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis MedComm cell metastasis ENKUR gastric cancer MYH9 |
| title | RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis |
| title_full | RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis |
| title_fullStr | RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis |
| title_full_unstemmed | RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis |
| title_short | RETRACTED: ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis |
| title_sort | retracted enkur recruits fbxw7 to ubiquitinate and degrade myh9 and further suppress myh9 induced deubiquitination of β catenin to block gastric cancer metastasis |
| topic | cell metastasis ENKUR gastric cancer MYH9 |
| url | https://doi.org/10.1002/mco2.185 |
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