TCP1 Regulates PI3K/AKT/mTOR Signalling Pathway to Promote Ovarian Cancer Cell Proliferation

Abstract ObjectiveTCP1 is one of the eight subunits of the TCP1 ring complex (TRiC) or the multi-protein mammalian cytosolic chaperone complex. TRiC participates in protein folding and regulates the expression of multiple signalling proteins and cytoskeletal components in cells. Although the clinical importance of its subunits has been clarified in various carcinomas, the function of TCP1 in ovarian cancer (OC) remains unclear. We aimed to identify the association between the expression of TCP1 and epithelial ovarian cancer (EOC) development and patients’ prognosis, and explore the underlying mechanisms of TCP1 on the tumour progression of ovarian cancer cells.MethodsTCP1 protein expression was tested in the various ovarian tissues by immunohistochemistry (IHC), and the correlation between TCP1 expression and clinical physiologic or pathologic parameters of EOC patients was analyzed in this study. The relationship between TCP1 expression and ovarian cancer patients’ prognosis was collected and analyzed using the Kaplan-Meier (KM) Plotter online database. Then, the expression levels of TCP1 was tested in different OC cell lines by Western blot. Furthermore, a model using ovarian cancer cell line A2780 was constructed for studying the functions of TCP1 in human EOC cell growth, migration, and invasion. Finally, possible regulated signalling pathways were discussed.ResultsTCP1 protein expression in ovarian cancer or borderline tissue was significantly higher compared to that in benign ovarian tumours and normal ovarian tissue. The upregulated expression of TCP1 in ovarian cancer was positively associated with and the differentiation grade and FIGO stage, which predicted poor clinical outcomes. Compared with IOSE-80 cells, TCP1 protein was overexpressed in the A2780 cells. TCP1 knockdown using shRNA lentivirus inhibited cell viability in A2780 cells. Western blot showed that the phosphatidylinositol-3 kinase (PI3K) signalling pathway was activated in the tumour invasion of EOC driven by TCP1. ConclusionThe protein level of TCP1 is overexpressed in aggressive histologic types of epithelial ovarian cancer. Upregulated TCP1 is correlated with poor prognosis of patients and TCP1 may serve as a novel prognostic biomarker. The mechanism of cancer progression promoted by TCP1 upregulation may be linked to the PI3K signalling pathway activation and TCP1 may serve as a novel target for ovarian cancer treatment.