title: Dual Roles for Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) in Cancer Progression.
abstract: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) are members of the hnRNP family of RNA binding proteins that regulate alternative splicing events associated with epithelial phenotypes. These proteins play crucial roles during organogenesis, including craniofacial and epidermal development as well as branching morphogenesis in the lungs and salivary glands. Recent reports have also addressed their roles during cancer progression. Expression of ESRP proteins is low in normal epithelium but upregulated in carcinoma in situ and advanced carcinomas. Intriguingly, they are downregulated in invasive fronts. The plastic nature of ESRP expression suggests dual roles for them in cancer progression. Consistently, it has been shown that ESRPs suppress motility and anchorage-independent growth of cancer cells while supporting cell survival by enhancing resistance to reactive oxygen species. Regulatory circuits that fine-tune ESRP gene expression have recently emerged. Here, we summarize recent findings on the molecular mechanisms by which ESRPs exert positive as well as negative effects on cancer progression.
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, 408-3898, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hayakawa
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, 408-3898, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, 408-3898, Japan. kmiyazawa@yamanashi.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000072417:Protein Domains; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C539364:ESRP1 protein, human; C539365:ESRP2 protein, human; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species
keywords: Alternative splicing; CD44; Cell motility; Epithelial splicing regulatory protein; δ-crystallin enhancer binding protein