RT Journal Article
SR Electronic
T1 Rab25 Regulates Invasion and Metastasis in Head and Neck Cancer
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1375
OP 1388
DO 10.1158/1078-0432.CCR-12-2858
VO 19
IS 6
A1 Amornphimoltham, Panomwat
A1 Rechache, Kamil
A1 Thompson, Jamie
A1 Masedunskas, Andrius
A1 Leelahavanichkul, Kantima
A1 Patel, Vyomesh
A1 Molinolo, Alfredo
A1 Gutkind, J. Silvio
A1 Weigert, Roberto
YR 2013
UL http://clincancerres.aacrjournals.org/content/19/6/1375.abstract
AB Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the 10 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 the role of Rab25 in tumor cell 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 reexpression of Rab25 in a metastatic cell line is sufficient to block invasion in a three-dimensional 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. Conclusion: 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. Clin Cancer Res; 19(6); 1375–88. ©2013 AACR.