PTOV1 Exerts Pro-oncogenic Role in Colorectal Cancer by Modulating SQSTM1-Mediated Autophagic Degradation of p53

Background The incidence and mortality of colorectal cancer (CRC) are increasing rapidly worldwide. 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 (TCGA and GEO) and clinic CRC samples. The effects of PTOV1 on the tumor-associated phenotypes of CRC were detected by EdU-DNA synthesis assay, transwell assays, cell colony formation assay, CRC subcutaneous tumor model and CRC metastasis mouse models. Immunoprecipitation (IP) combined with protein mass spectrometry was used to identify potential molecules interacting with PTOV1. Co-Immunoprecipitation (Co-IP) was employed to validate the binding between PTOV1 and its interacting protein p53. 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 reveals an oncogenic role of PTOV1 in CRC progression, which was achieved by promoting SQSTM1 directed autophagic degradation of p53. This work may provide promising therapeutic targets for CRC.