Table of Contents

ABSTRACT

Head and Neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in men and has a poor prognosis. The molecular events leading to HNSCC need to be understood. We have identified by Differential Display many novel deregulated genes with unknown functions that require characterization. We show here that one of these genes, NUDCD2, is overexpressed in 70% of patients with HNSCC and in many HNSCC cell lines in culture. NUDCD2 RNA and protein localize to tumour cell islets of human HNSCC compared to surrounding stromal tissue. NUDCD2 overexpression in cells alters cell and nuclear shapes, and induces multinucleation. Time-lapse microscopy showed that there are mitotic aberrations and retention of nucleoplasmic bridges (NPB) between un-separated nuclei following abnormal mitosis. NUDCD2 possesses a p23-like domain, linking NUDCD2 to a family of proteins related to p23, a co-chaperone for Hsp90. Interestingly, the NUDCD2 C-terminal region is also highly similar to the Nuclear Move domain of NudC, a protein involved in the nuclear migration cycle and whose overexpression provokes multinucleation. Furthermore, we found that both proteins colocalize in the Golgi apparatus. These findings suggest that NUDCD2 is a new member of the NudC sub-family that plays an important role in the reformation and maintenance of nuclear integrity following mitosis. Imbalances in the levels of NUDCD2 could be evaluated as a factor contributing to chromosomal instability in HNSCC through effects on the complex processes of mitosis and cell division.

Keywords: HNSCC, overexpression, multinucleation, NudC.