CDCA5 promotes the progression of prostate cancer by affecting the ERK signalling pathway

Abstract

Cell division cycle-associated 5 (CDCA5) can regulate cell cycle-related proteins to promote the proliferation of cancer cells. The purpose of the present study was to investigate the expression level of CDCA5 in prostate cancer (PCa) and its effect on PCa progression. The signalling pathway by which CDCA5 functions through was also attempted to elucidate. Clinical specimens of PCa patients were collected from the Second Hospital of Tianjin Medical University. The expression level of CDCA5 in cancer tissues and paracancerous tissues from PCa patients was detected by RT-qPCR analysis and IHC. The relationship between the expression level of CDCA5 and the survival rate of PCa patients was analysed using TCGA database. Two stable cell lines (C4-2 and PC-3) with CDCA5 knockdown were established, and the effects of CDCA5 on PCa cell proliferation were detected by MTT and colony formation assays. Flow cytometry was performed to detect the effect of CDCA5 on the PCa cell division cycle, and western blot analysis was used to determine changes in ERK phosphorylation levels after CDCA5 knockdown. The effect of CDCA5 expression on prostate tumour growth was assessed using a mouse xenograft model. The results revealed that the mRNA and protein expression levels of CDCA5 were significantly higher in PCa tissues than in paracancerous tissues. High CDCA5 expression was associated with the prognosis of patients with PCa. CDCA5 expression knockdown significantly reduced the number of PCa cells in mitoses and inhibited their proliferation in vitro and in vivo . When CDCA5 was knocked down, the phosphorylation level of ERK was also reduced. Collectively, CDCA5 was upregulated and affected the prognosis of patients with PCa. Decreased CDCA5 expression inhibited PCa cell proliferation by inhibiting the ERK signalling pathway. Thus, CDCA5 may be a potential therapeutic target for PCa.

Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer

“…Nonetheless, this study also showed that high CDCA5 expression was significantly associated with an increase in cell cycle activity markers such as Ki67 and Cyclin B1. This in consistent with a previous study by Ji et al, which indicated that high CDCA5 expression is associated with poor survival in prostate cancer [ 45 ] Furthermore, our functional results suggest that decreasing CDCA5 occurs with an accumulation of cells in the G2/M phase of cell cycle in aggressive tumors. This may be explained by pro-oncogenic role of CDCA5 during the cell cycle that impairs cancer apoptosis while promoting cell proliferation via the PI3K/AKT/mTOR signalling pathway, which was shown on our results at transcriptomic level.…”

Suppression of CDCA3 inhibits prostate cancer progression via NF‑κB/cyclin D1 signaling inactivation and p21 accumulation

“…Abnormal cell division can lead to cancer. Disturbance of cell cycle regulation is an important biological feature exhibited in malignant tumors and can lead to reduced apoptosis, unlimited proliferation and metastasis in malignant cells (30). CDCA3 belongs to a family of cell division-associated proteins, which function as part of the SKP1-Cullin-RING-F-box ubiquitin ligase complex that mediates the destruction of the mitosis-inhibitory kinase wee1 (14,16).…”

Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non‐small cell lung cancer cells via p53‐p21 signaling pathway

“…There is now growing evidence that CDCA5 is overexpressed as an oncogene in a variety of common malignancies and has been proven to play a crucial part in tumorigenesis and development, including NSCLC, 13 hepatocellular carcinoma, 14 , 15 prostate cancer, 16 , 17 gastric cancer, 18 , 19 ovarian cancer, 20 nasopharyngeal carcinoma, 21 bladder cancer, 22 esophageal squamous cell carcinoma, 23 colorectal cancer, 24 breast cancer, 25 oral squamous cell carcinoma. 26 So far, only Nguyen et al have discussed the relationship between CDCA5 and NSCLC in detail, and they reported that CDCA5, recognized as an independent prognostic factor of NSCLC, played an essential role in the growth of lung cancer cells.…”