Ataxia-telangiectasia mutated interactor regulates head and neck cancer metastasis via KRas expression. (March 2017)

• Record Type: Journal Article
• Authors: Li, Yue-Ju; Lai, Wei-Ting; Chang, Cheng-Chi; Kuo, Mark Yen-Ping; Deng, Yi-Ting; Yang, Cheng-Ning; Cheng, Shih-Jung; Wu, Tai-Sheng; Chen, Szu-Ta; Lin, Been-Ren
• Is Part Of: Oral oncology. Volume 66(2017)
• Page Start: 100
• Page End: 107
• Publication Date: 2017-03
• Subjects: HNSCC head and neck squamous cell carcinoma -- ATMIN ataxia-telangiectasia mutated interactor; ATMIN -- HNSCC -- Metastasis -- KRas; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2016.11.006
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: ATMIN is highly expressed in late-stage HNSCC patients' tumors. Knock-down of ATMIN in HNSCC cell line reduces the ability of lymph-node metastasis. KRas is firstly identified as a ATMIN's downstream target and an oncogene in HNSCC. Abstract: Objectives: 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. Materials and methods: 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. Results: 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. Conclusions: 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.