title: Ataxia-telangiectasia mutated interactor regulates head and neck cancer metastasis via KRas expression.
abstract: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear.
  
  
  
  ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided.
  
  
  
  ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression.
  
  
  
  The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan; Angiogenesis Research Center, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Yue-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Lai
authors.affiliation: Angiogenesis Research Center, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taiwan; Department of Biotechnology, Asia University, Taiwan.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Mark Yen-Ping
authors.initials: MY
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Deng
authors.affiliation: Angiogenesis Research Center, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Cheng-Ning
authors.initials: CN
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taiwan.
authors.forename: Tai-Sheng
authors.initials: TS
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Szu-Ta
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Angiogenesis Research Center, National Taiwan University, Taiwan; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: beenrenlin@ntu.edu.tw.
authors.forename: Been-Ren
authors.initials: BR
authors.lastname: Lin
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D011905:Genes, ras; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C522841:ATMIN protein, human; D014157:Transcription Factors
keywords: ATMIN; HNSCC; KRas; Metastasis