24P - CDCA3 regulates the cell cycle and modulates cisplatin sensitivity in non-small cell lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer Agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Kenneth O'Byrne
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. O'Byrne1, M. Adams2, J. Burgess2, D. Richard2
  • 1Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, 4102 - Brisbane/AU
  • 2Institute Of Health And Biomedical Innovation, Cancer And Ageing Research Program, Queensland University of Technology, Brisbane/AU



Cisplatin-based regimens are currently the most effective chemotherapy for non-small cell lung cancer (NSCLC). Cisplatin forms DNA crosslinks to stall DNA replication and induce apoptosis. However, intrinsic and acquired chemoresistance is a major therapeutic problem. We have identified ‘cell division cycle associated protein 3’ (CDCA3) as a novel protein that may prove useful in delaying or preventing cisplatin resistance in NSCLC. CDCA3 functions as part of an ubiquitin ligase complex to degrade the endogenous cell cycle inhibitors. While a role for CDCA3 in disease is emerging with elevated expression noted in oral squamous cell carcinoma, little else is known about CDCA3 or whether this protein may prove useful clinically.


CDCA3 expression was assessed in NSCLC using bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets. CDCA3 function was examined using siRNA-based approach in immortalized lung epithelial (HBEC4) and fibroblast (CCL75) cells and in a range of NSCLC cells lines (A549, H2228, HCC827, H460, SKMES-1, CRL5889, HTB189 and EBC-1 cells). Cell proliferation was examined using an Incucyte Zoom (Essen Biosciences). Cell cycle progression was assessed using a Beckman Coulter Gallios flow cytometer. Cell viability was assessed following cisplatin treatment using the CellTitre-Glo assay (Promega).


Bioinformatic analysis of The Cancer Genome Atlas indicates that CDCA3 is markedly elevated in NSCLC and this elevated expression is associated with poor patient outcome. Depletion of CDCA3 in a range of NSCLC cell lines (A549, H2228, HCC827, H460, SKMES-1, CRL5889, HTB189 and EBC-1 cells) markedly impairs proliferation by inducing cell cycle arrest in the G2 phase of the cell cycle but not in lung fibroblast (CCL75) or in immortalized human bronchial epithelial cells (HBEC4). Most interestingly, siRNA-mediated CDCA3 depletion also enhances NSCLC cell but not HBEC4 cell line sensitivity to cisplatin.


Our data highlight CDCA3 as a novel factor in mediating NSCLC cell proliferation and sensitivity to cisplatin. Further identifying the molecular regulation of CDCA3 may yield novel therapeutic avenues in combination with cisplatin in NSCLC.

Clinical trial identification

Legal entity responsible for the study

Queensland University of Technology


Queensland Health, Australia; National Health and Medical Research Council, Australia


All authors have declared no conflicts of interest.