title: Dnajb8, a Member of the Heat Shock Protein 40 Family Has a Role in the Tumor Initiation and Resistance to Docetaxel but Is Dispensable for Stress Response.
abstract: Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined by their abilities of tumor initiation, self-renewal and differentiation. In a previous study, we showed by gene knockdown using siRNA and gene overexpression experiments that Dnaj (Hsp40) homolog, subfamily B, member 8 (DNAJB8), a role in the maintenance, of renal cell carcinoma CSCs/CICs. In the present study, we established Dnajb8 knockout (KO) renal cell carcinoma (RCC) line cells (RenCa cells) and analyzed the cells to confirm the function of Dnajb8 in RCC CSCs/CICs. Dnajb8 KO cells showed reduced ratios of side population cells and reduced sphere forming ability. An in vivo single cell tumor initiation assay revealed that the numbers of CSCs/CICs were 3 in 4 wild-type RenCa cells and 1 in 4 Dnajb8 KO cells. Dnajb8 KO cells showed sensitivity to Docetaxel. On the other hand, Dnajb8 KO cells did not show any sensitivities to stresses including low pH, low glucose, heat shock and sensitivity to cisplatin. The results indicate that Dnajb8 has a role in tumor initiation, side population ratio and sphere formation but it is dispensable for stress responses.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.|Department of Veterinary Diagnostic Imaging, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kusumoto
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Murai
authors.affiliation: Department of Veterinary Diagnostic Imaging, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Imagawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D002292:Carcinoma, Renal Cell / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D055786:Gene Knockout Techniques; D005947:Glucose / Q000737:chemistry; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D058985:Side-Population Cells / Q000378:metabolism; D013312:Stress, Physiological; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C582953:DNAJB8 protein, human; C000609095:Dnajb8 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D005947:Glucose; D002945:Cisplatin