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

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146501-e0146501
• Main Authors: Yamashita, Masamichi, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Kusumoto, Hiroki, Murai, Aiko, Imagawa, Tomohiro, Sato, Noriyuki
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Base Sequence; Brain cancer; Cancer; Carcinoma, Renal Cell - pathology; Cell Differentiation; Cell Line, Tumor; Cell self-renewal; Cell Transformation, Neoplastic - metabolism; Cisplatin; Cisplatin - therapeutic use; Colorectal cancer; CRISPR; CRISPR-Cas Systems; Deoxyribonucleic acid; DNA; Docetaxel; Drug Resistance, Neoplasm; Female; Gene expression; Gene Knockout Techniques; Genomes; Glucose - chemistry; Heat shock proteins; Homology; HSP40 Heat-Shock Proteins - metabolism; Hsp40 protein; Humans; Hydrogen-Ion Concentration; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Medical research; Metastasis; Mice; Mice, Inbred BALB C; Molecular Chaperones - metabolism; Molecular Sequence Data; Neoplasm Transplantation; Neoplastic Stem Cells - cytology; Nerve Tissue Proteins - metabolism; Pathology; Renal cell carcinoma; RNA, Small Interfering - metabolism; Sensitivity; Side-Population Cells - metabolism; siRNA; Stem cells; Stress, Physiological; Taxoids - therapeutic use; Tumors; Veterinary colleges; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146501

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.