PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53
Abstract Background Prostate Tumor Overexpressed 1 (PTOV1) is overexpressed and associated with malignant phenotypes in various types of tumors. However, the detailed roles of PTOV1 and its underlying mechanism in CRC remain unclear. Methods The clinical significance of PTOV1 was assessed in clinica...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06179-x |
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| author | Yongli Fan Yuqin Li Xia Luo Shiqi Xiang Jia Hu Jingchun Zhan Weilong Chang Rui Deng Xianwen Ran Yize Zhang Yudie Cai Weiwei Zhu Huifen Wang Zhibo Liu Di Wang |
| author_facet | Yongli Fan Yuqin Li Xia Luo Shiqi Xiang Jia Hu Jingchun Zhan Weilong Chang Rui Deng Xianwen Ran Yize Zhang Yudie Cai Weiwei Zhu Huifen Wang Zhibo Liu Di Wang |
| author_sort | Yongli Fan |
| collection | DOAJ |
| description | Abstract Background Prostate Tumor Overexpressed 1 (PTOV1) is overexpressed and associated with malignant phenotypes in various types of tumors. However, the detailed roles of PTOV1 and its underlying mechanism in CRC remain unclear. Methods The clinical significance of PTOV1 was assessed in clinical databases and CRC samples. The effects of PTOV1 on the tumor-associated phenotypes of CRC were detected by several in vitro assays and in vivo mouse models. Immunoprecipitation (IP) combined with protein mass spectrometry and Co-Immunoprecipitation (Co-IP) was used to identify p53 interacting with PTOV1. Immunofluorescence assay, western blot and transmission electron microscopy (TEM) analysis were used to evaluated the effects of PTOV1 on autophagy. Results Here, we revealed that PTOV1 was highly expressed in human CRC tissues, especially at advanced stages, and associated with reduced survival time among CRC patients. The upregulated PTOV1 promoted cell proliferation, migration, invasion, tumor growth and metastasis of CRC cells in vitro and in vivo. At the molecular level, PTOV1 destabilized p53 by activating autophagy and recruiting p53 for the cargo receptor SQSTM1 directed autophagic degradation. There was a negative expression correlation between PTOV1 and p53 in CRC tissues. Moreover, p53 overexpression or SQSTM1 knockdown reversed the pro-tumor phenotypes of PTOV1 in CRC. Conclusion Our study unveils the oncogenic role of PTOV1 in CRC progression, which was achieved by promoting SQSTM1 directed autophagic degradation of p53. These findings highlight the potential of targeting the PTOV1-SQSTM1-p53 axis as a therapeutic approach for CRC. |
| format | Article |
| id | doaj-art-fb8af5850a2d43b493d55ee28f4c4e76 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-fb8af5850a2d43b493d55ee28f4c4e762025-02-09T12:52:20ZengBMCJournal of Translational Medicine1479-58762025-02-0123111610.1186/s12967-025-06179-xPTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53Yongli Fan0Yuqin Li1Xia Luo2Shiqi Xiang3Jia Hu4Jingchun Zhan5Weilong Chang6Rui Deng7Xianwen Ran8Yize Zhang9Yudie Cai10Weiwei Zhu11Huifen Wang12Zhibo Liu13Di Wang14Department of Oncology, the First Affiliated Hospital of Henan UniversityDepartment of Medical Laboratory, Tongji Medical College, the Central Hospital of Wuhan, Huazhong University of Science and TechnologyDepartment of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and TechnologyInstitute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and TechnologyCollege of Anesthesiology, Xinxiang Medical UniversityDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou UniversityTranslational Medicine Center, the First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, the First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, the First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, the First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou UniversityAbstract Background Prostate Tumor Overexpressed 1 (PTOV1) is overexpressed and associated with malignant phenotypes in various types of tumors. However, the detailed roles of PTOV1 and its underlying mechanism in CRC remain unclear. Methods The clinical significance of PTOV1 was assessed in clinical databases and CRC samples. The effects of PTOV1 on the tumor-associated phenotypes of CRC were detected by several in vitro assays and in vivo mouse models. Immunoprecipitation (IP) combined with protein mass spectrometry and Co-Immunoprecipitation (Co-IP) was used to identify p53 interacting with PTOV1. Immunofluorescence assay, western blot and transmission electron microscopy (TEM) analysis were used to evaluated the effects of PTOV1 on autophagy. Results Here, we revealed that PTOV1 was highly expressed in human CRC tissues, especially at advanced stages, and associated with reduced survival time among CRC patients. The upregulated PTOV1 promoted cell proliferation, migration, invasion, tumor growth and metastasis of CRC cells in vitro and in vivo. At the molecular level, PTOV1 destabilized p53 by activating autophagy and recruiting p53 for the cargo receptor SQSTM1 directed autophagic degradation. There was a negative expression correlation between PTOV1 and p53 in CRC tissues. Moreover, p53 overexpression or SQSTM1 knockdown reversed the pro-tumor phenotypes of PTOV1 in CRC. Conclusion Our study unveils the oncogenic role of PTOV1 in CRC progression, which was achieved by promoting SQSTM1 directed autophagic degradation of p53. These findings highlight the potential of targeting the PTOV1-SQSTM1-p53 axis as a therapeutic approach for CRC.https://doi.org/10.1186/s12967-025-06179-xColorectal cancerAutophagyPTOV1p53 |
| spellingShingle | Yongli Fan Yuqin Li Xia Luo Shiqi Xiang Jia Hu Jingchun Zhan Weilong Chang Rui Deng Xianwen Ran Yize Zhang Yudie Cai Weiwei Zhu Huifen Wang Zhibo Liu Di Wang PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 Journal of Translational Medicine Colorectal cancer Autophagy PTOV1 p53 |
| title | PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 |
| title_full | PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 |
| title_fullStr | PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 |
| title_full_unstemmed | PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 |
| title_short | PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 |
| title_sort | ptov1 exerts pro oncogenic role in colorectal cancer by modulating sqstm1 mediated autophagic degradation of p53 |
| topic | Colorectal cancer Autophagy PTOV1 p53 |
| url | https://doi.org/10.1186/s12967-025-06179-x |
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