Rab25 regulates invasion and metastasis in head and neck cancer
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par une enzyme, Rab25, dans le processus métastatique d'un carcinome épidermoïde de la tête et du cou
Purpose:Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers with a 50% five-year survival rate, which has remained unchanged for the past three decades. One of the major reasons for the aggressiveness of this cancer is that HNSCCs readily metastasize to cervical lymph nodes that are abundant in the head and neck region. Hence, discovering new molecules controlling the metastatic process as well as understanding their regulation at the molecular level are essential for effective therapeutic strategies. Experimental Design:Rab25 expression level was analyzed in HNSCC tissue microarray. We used a combination of intravital microscopy in live animals and immunofluorescence in an in vitro invasion assay, to study role of Rab25 in tumor cells migration and invasion. Results:In this study, we identified the small GTPase Rab25 as a key regulator of HNSCC metastasis. We observed that Rab25 is downregulated in HNSCC patients. Next, we determined that re-expression of Rab25 in a metastatic cell line is sufficient to block invasion in a 3D collagen matrix and metastasis to cervical lymph nodes in a mouse model for oral cancer. Specifically, Rab25 affects the organization of F-actin at the cell surface, rather than cell proliferation, apoptosis or tumor angiogenesis. Conclusions:These findings suggest that Rab25 plays an important role in tumor migration and metastasis, and that understanding its function may lead to the development of new strategies to prevent metastasis in oral cancer patients.