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

Abstract

Background: Cell Division Cycle Associated 5 (CDCA5) plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biological value of CDCA5 in breast cancer (BC). Methods: The biological and prognostic value of CDCA5 were evaluated at mRNA (n = 5109) and protein levels (n = 614) utilizing multiple well-characterized early stage BC cohorts. The effects of CDCA5 knockdown (KD) on multiple oncogenic assays were assessed in vitro using a panel of BC cell lines. Results: this study examined cohorts showed that high CDCA5 expression was correlated with features characteristic of aggressive behavior and poor prognosis, including the presence of high grade, large tumor size, lymphovascular invasion (LVI), hormone receptor negativity and HER2 positivity. High CDCA5 expression, at both mRNA and protein levels, was associated with shorter BC-specific survival independent of other variables (p = 0.034, Hazard ratio (HR) = 1.6, 95% CI; 1.1–2.3). In line with the clinical data, in vitro models indicated that CDCA5 depletion results in a marked decrease in BC cell invasion and migration abilities and a significant accumulation of the BC cells in the G2/M-phase. Conclusions: These results provide evidence that CDCA5 plays an important role in BC development and metastasis and could be used as a potential biomarker to predict disease progression in BC.

CDCA5-EEF1A1 interaction promotes progression of clear cell renal cell carcinoma by regulating mTOR signaling

“…We next investigated the potential mechanisms of CDCA5-mediated ccRCC progression. The activation of CDCA5 has been reported to induce breast tumor progression via PI3K-AKT-mTOR signaling pathway [ 12 , 16 ]. As well-characterized PI3K-AKT-mTOR effectors, the phosphorylation and activation of AKT, 4E-BP1 and S6 regulates cell survival, proliferation, and growth [ 17 ].…”

The impact of CDCA5 expression on the immune microenvironment and its potential utility as a biomarker for PD-L1/PD-1 inhibitors in lung adenocarcinoma

“…CDCA5 regulates sister chromatid cohesion and plays essential roles in mitosis [ 7 ]. CDCA5 expression is associated with poor prognosis in several cancers [ [10] , [11] , [12] , [13] ]. CDCA5 has been reported to be associated with cell proliferation, apoptosis, and cell cycle arrest; however, its relevance to the immune microenvironment has not been well studied [ 7 , 35 ].…”

“…Several recent studies have reported that CDCA5 may play a role in cancer progression. High levels of CDCA5 are associated with worse outcomes in patients with cancers, such as lung [ 10 ], breast [ 11 ], gastric [ 12 ] and prostate cancers [ 13 ].…”