Fan Yongli, Li Yuqin, Luo Xia, Xiang Shiqi, Hu Jia, Zhan Jingchun, Chang Weilong, Deng Rui, Ran Xianwen, Zhang Yize, Cai Yudie, Zhu Weiwei, Wang Huifen, Liu Zhibo, Wang Di
Department of Oncology, the First Affiliated Hospital of Henan University, Kaifeng, 475000, China.
Department of Medical Laboratory, Tongji Medical College, the Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Transl Med. 2025 Feb 4;23(1):157. doi: 10.1186/s12967-025-06179-x.
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.
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.
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.
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.
前列腺肿瘤过表达蛋白1（PTOV1）在多种肿瘤中呈过表达状态，并与恶性表型相关。然而，PTOV1在结直肠癌中的具体作用及其潜在机制仍不清楚。
在临床数据库和结直肠癌样本中评估PTOV1的临床意义。通过多种体外实验和体内小鼠模型检测PTOV1对结直肠癌肿瘤相关表型的影响。采用免疫沉淀（IP）结合蛋白质质谱分析以及免疫共沉淀（Co-IP）来鉴定与PTOV1相互作用的p53。利用免疫荧光实验、蛋白质免疫印迹法和透射电子显微镜（TEM）分析来评估PTOV1对自噬的影响。
在此，我们发现PTOV1在人类结直肠癌组织中高表达，尤其是在晚期阶段，并且与结直肠癌患者生存时间缩短相关。上调的PTOV1在体外和体内均促进了结直肠癌细胞的增殖、迁移、侵袭、肿瘤生长和转移。在分子水平上，PTOV1通过激活自噬并募集p53用于货物受体SQSTM1介导的自噬降解，从而使p53不稳定。在结直肠癌组织中，PTOV1与p53之间存在负表达相关性。此外，p53过表达或SQSTM1敲低可逆转PTOV1在结直肠癌中的促肿瘤表型。
我们的研究揭示了PTOV1在结直肠癌进展中的致癌作用，这是通过促进SQSTM1介导的p53自噬降解实现的。这些发现凸显了靶向PTOV1-SQSTM1-p53轴作为结直肠癌治疗方法的潜力。
