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

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...

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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
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cited_by cdi_FETCH-LOGICAL-c758t-867cdf6664e4f3c516010a66173baff6d421503713605647880e577fe19136b73
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container_issue 1
container_start_page e0146501
container_title PloS one
container_volume 11
creator Yamashita, Masamichi
Hirohashi, Yoshihiko
Torigoe, Toshihiko
Kusumoto, Hiroki
Murai, Aiko
Imagawa, Tomohiro
Sato, Noriyuki
description 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.
doi_str_mv 10.1371/journal.pone.0146501
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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26751205</pmid><doi>10.1371/journal.pone.0146501</doi><oa>free_for_read</oa></addata></record>
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issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1757044044
source Publicly Available Content Database; PubMed Central
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
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
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