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Rab25 regulates invasion and metastasis in head and neck cancer.

AbstractPURPOSE:
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.
AuthorsPanomwat Amornphimoltham, Kamil Rechache, Jamie Thompson, Andrius Masedunskas, Kantima Leelahavanichkul, Vyomesh Patel, Alfredo Molinolo, J Silvio Gutkind, Roberto Weigert
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 6 Pg. 1375-88 (Mar 15 2013) ISSN: 1078-0432 [Print] United States
PMID23340300 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Actins
  • Rab25 protein, human
  • rab GTP-Binding Proteins
Topics
  • Actins (metabolism)
  • Animals
  • Carcinoma, Squamous Cell (genetics, pathology)
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Head and Neck Neoplasms (genetics, pathology)
  • Humans
  • Lymphatic Metastasis (genetics, pathology)
  • Mice
  • Neoplasm Invasiveness (genetics, pathology)
  • Tissue Array Analysis
  • Tongue Neoplasms (genetics, pathology)
  • Xenograft Model Antitumor Assays
  • rab GTP-Binding Proteins (genetics, metabolism)

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