title: Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in human maxillary cancer cells.
abstract: Cisplatin plays an important role in the therapy for human head and neck cancers. However, cancer cells develop cisplatin resistance, leading to difficulty in treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3 cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin-induced apoptosis through induction of G2/M arrest, which allows cancer cells to repair damaged DNA and survive. In the present study, we specifically examined Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A, resulting in G2/M arrest. PCBP4 plays important roles in the induction of cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular target for the therapy of head and neck cancers, especially cisplatin-resistant cancers.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Narita
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medical Sciences, University of Oita.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Nomi
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Chizuru
authors.initials: C
authors.lastname: Sugimoto
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Takechiyo
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Bioresearch, Life Science Research Laboratory, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Karaya
authors.affiliation: Division of Oncology, Biomedical Imaging Research Center, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D008441:Maxillary Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020687:cdc25 Phosphatases / Q000235:genetics
chemical_list: C411734:PCBP4 protein, human; D016601:RNA-Binding Proteins; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D002945:Cisplatin