title: High level expression of AMAP1 protein correlates with poor prognosis and survival after surgery of head and neck squamous cell carcinoma patients.
abstract: BACKGROUND
  Despite recent advances in cancer therapeutics in general, the survival of patients with head and neck squamous cell carcinomas (HNSCCs) has not improved substantially over the past few decades. HNSCC cells often exhibit invasive and metastatic phenotypes, and expression of epidermal growth factor receptor (EGFR) and cortactin has been highly implicated in the development of malignancy in HNSCCs. We have shown previously that an Arf6 pathway, in which Arf6 is activated by GEP100 and employs AMAP1 (also called DDEF1 or ASAP1) as its downstream effector, is pivotal for the invasion and metastasis of different breast cancer cells. This pathway is activated by receptor tyrosine kinases, including EGFR; and moreover, AMAP1 physically associates with cortactin, in which inhibition of this binding effectively blocks invasion and metastasis. We here investigated whether the expression of Arf6 pathway components correlates with the poor prognosis of HNSCC patients. We have shown previously that AMAP1 protein levels are not correlated with its mRNA levels, and hence we here employed immunohistochemical staining of HNSCC clinical specimens to investigate AMAP1 protein levels.
  
  
  RESULTS
  We found that high levels of AMAP1 protein expression on its own, as well as its co-overexpression with EGFR statistically correlates with poor disease-free survival and poor overall survival, while high levels of cortactin expression or its co-expression with EGFR did not.
  
  
  CONCLUSIONS
  Our identification of predictive biomarkers, together with our previous findings on the coherent signaling pathway that these biomarkers ultimately generate should be powerful information for the further development of HNSCC therapeutics.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Kanako C
authors.initials: KC
authors.lastname: Hatanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hatakeyama
authors.forename: Ari
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Molecular Biology, Hokkaido University Graduate School of Medicine, W15N7 Kitaku, Sapporo 060-838, Japan. sabeh@med.hokudai.ac.jp.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Sabe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors