title: Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma.
abstract: Chromosomal amplifications of the 11q13 genomic region are frequent in head and neck squamous cell carcinoma (HNSCC). To identify novel 11q13 amplification targets, we integrated high-resolution array-based comparative genomic hybridization and Affymetrix gene-expression profiling of eight HNSCC cell lines. We found that PPFIA1 was the highest upregulated gene in the 11q13 amplicon of HNSCC cell lines when compared with HNSCC lines without 11q13 amplification and confirmed the upregulation of PPFIA1 in primary HNSCCs by real-time PCR. Using siRNA knockdown, we investigated PPFIA1 function in three HNSCC lines using both in vitro invasion assays and wound-healing assays. Surprisingly, we found that cancer cells become more invasive when the PPFIA1 protein levels were reduced, suggesting that PPFIA1 may act as an invasion inhibitor in HNSCC. This unexpected result suggests that the 11q13 amplicon may comprise both positive and negative regulators involved in HNSCC. Our study is the first to evaluate the role of PPFIA1 in head and neck carcinogenesis and suggests a potential link between PPFIA1 activity and cell-extracellular matrix interactions. This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore.
authors.forename: Kaia Davis
authors.initials: KD
authors.lastname: Tan
authors.forename: Yansong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hiang Khoon
authors.initials: HK
authors.lastname: Tan
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.forename: Amit
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Jeanie
authors.initials: J
authors.lastname: Wu
authors.forename: Hui Yong
authors.initials: HY
authors.lastname: Wu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hwang
authors.forename: Dennis T H
authors.initials: DT
authors.lastname: Lim
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018450:Disease Progression; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C094398:PPFIA1 protein, human; D034741:RNA, Small Interfering