title: Rab25 regulates invasion and metastasis in head and neck cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
authors: Intracellular Membrane Trafficking Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4340, USA.
authors: Panomwat
authors: P
authors: Amornphimoltham
authors: Kamil
authors: K
authors: Rechache
authors: Jamie
authors: J
authors: Thompson
authors: Andrius
authors: A
authors: Masedunskas
authors: Kantima
authors: K
authors: Leelahavanichkul
authors: Vyomesh
authors: V
authors: Patel
authors: Alfredo
authors: A
authors: Molinolo
authors: J Silvio
authors: JS
authors: Gutkind
authors: Roberto
authors: R
authors: Weigert
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; C509763:Rab25 protein, human; D020691:rab GTP-Binding Proteins