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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
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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
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Journal Article
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
2016
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antineoplastic Agents - therapeutic use
/ Cancer
/ Carcinoma, Renal Cell - pathology
/ Cell Transformation, Neoplastic - metabolism
/ CRISPR
/ DNA
/ Female
/ Genomes
/ Homology
/ HSP40 Heat-Shock Proteins - metabolism
/ Humans
/ Kidney Neoplasms - drug therapy
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Mice
/ Molecular Chaperones - metabolism
/ Neoplastic Stem Cells - cytology
/ Nerve Tissue Proteins - metabolism
/ RNA, Small Interfering - metabolism
/ Side-Population Cells - metabolism
/ siRNA
/ Tumors
