title: Epithelial splicing regulatory proteins 1 (ESRP1) and 2 (ESRP2) suppress cancer cell motility via different mechanisms.
abstract: ESRP1 (epithelial splicing regulatory protein 1) and ESRP2 regulate alternative splicing events associated with epithelial phenotypes of cells, and both are down-regulated during the epithelial-mesenchymal transition. However, little is known about their expression and functions during carcinogenesis. In this study, we found that expression of both ESRP1 and ESRP2 is plastic: during oral squamous cell carcinogenesis, these proteins are up-regulated relative to their levels in normal epithelium but down-regulated in invasive fronts. Importantly, ESRP1 and ESRP2 are re-expressed in the lymph nodes, where carcinoma cells metastasize and colonize. In head and neck carcinoma cell lines, ESRP1 and ESRP2 suppress cancer cell motility through distinct mechanisms: knockdown of ESRP1 affects the dynamics of the actin cytoskeleton through induction of Rac1b, whereas knockdown of ESRP2 attenuates cell-cell adhesion through increased expression of epithelial-mesenchymal transition-associated transcription factors. Down-regulation of ESRP1 and ESRP2 is thus closely associated with a motile phenotype of cancer cells.
authors.affiliation: From the Departments of Biochemistry, Otolaryngology, Head and Neck Surgery, and.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: From the Departments of Biochemistry.
authors.forename: Masao
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: the Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-0034, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Human Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898 and.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Human Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898 and.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
authors.affiliation: Otolaryngology, Head and Neck Surgery, and.
authors.forename: Shota
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: From the Departments of Biochemistry.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Motizuki
authors.affiliation: Otolaryngology, Head and Neck Surgery, and.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
authors.affiliation: From the Departments of Biochemistry, kmiyazawa@yamanashi.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C539364:ESRP1 protein, human; C539365:ESRP2 protein, human; D016601:RNA-Binding Proteins
keywords: Cancer Biology; Cell Invasion; Cell Motility; ESRP; Epithelial-Mesenchymal Transition (EMT); RNA Splicing; Rac1b; SIP1; δEF1