1. ¹Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
2. ²Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan
3. ³Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
4. ⁴Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
5. ⁵Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

Correspondence: Dr C-Y Chien, Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, No. 123, Ta-Pei Road, Niao Sung Hsiang, Kaohsiung 833, Taiwan. E-mail: cychien3965@adm.cgmh.org.tw; Dr C-YF Huang, Institute of Clinical Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 115, Taiwan. E-mail: cyhuang5@ym.edu.tw

Received 26 November 2008; Revised 17 April 2009; Accepted 26 April 2009; Published online 15 June 2009.

Abstract

Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interefering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.