Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

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.

Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study

“…Several pathways have been proposed and recent studies have pointed to a considerable role for FOXM1 in invasion and metastasis [8,26]. It FOXM1 has been shown to regulate transcription of c-Jun N-terminal kinase ( JNK1) gene to promote the G1/S transition and tumor cell invasiveness, partly by upregulating the expression of the matrix metalloproeinases (MMPs) 2 and MMP9, both of which are crucial in the processes of tumor cell invasion and metastasis for MMPs can directly degrade the basement membrane collagen at tumorinvasive front and enable cancer cells to overcome the extracellular matrix (ECM) barrier leading to metastasis [27,28]. In lung cancer cells, combining radiation therapy with MMP2 down regulation is more e ective than radiation alone, and such a strategy involves abrogation of FOXM1 activity [29].…”

MnSOD Promotes Tumor Invasion via Upregulation of FoxM1–MMP2 Axis and Related with Poor Survival and Relapse in Lung Adenocarcinomas

“…Several studies have implicated FoxM1 in tumorigenesis, as it is overexpressed in various human cancers including lung cancer (24)(25)(26)(27)(28). Wang and colleagues showed that proliferation of lung tumor cells was diminished in Mx-Cre FoxM1 À/À mouse mutants and that these mice had a significant reduction in the number and size of lung adenomas (28).…”

Reduced expression of TRF1 is associated with tumor progression and poor prognosis in oral squamous cell carcinoma

“…investigation of OcScc progression from a genetic perspective has identified distinct patterns and timings of genetic alterations (3). the most important prognostic factors in OcScc are those that form part of the grading system, including tumor stage and lymph node status (4)(5)(6). The identification of new prognostic factors linked to OcScc initiation and progression may aid in the development of new diagnostic tools and treatment strategies.…”