A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer

• Published in: Scientific reports 2017-08, Vol.7 (1), p.10228-10228, Article 10228
• Main Authors: Gasa, L., Sanchez-Botet, A., Quandt, E., Hernández-Ortega, S., Jiménez, J., Carrasco-García, M. A., Simonetti, S., Kron, S. J., Ribeiro, M. P., Nadal, E., Villanueva, A., Clotet, J.
• Format: Article
• Language: English
• Subjects: 13/51; 631/67/1612/1350; 631/67/395; 64/60; 692/53/2422; 82/80; 96/109; A549 Cells; Animals; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cyclins; Cyclins - metabolism; Gene expression; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mice; multidisciplinary; Neoplasm Transplantation; Paraffin; Prognosis; Science; Science (multidisciplinary); Survival Analysis; Tumor cell lines; Tumors; Up-Regulation; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10770-8

As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients’ stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease.