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Cellular stress induces cancer stem‐like cells through expression of DNAJB8 by activation of heat shock factor 1
- Source :
- Cancer Science
- Publication Year :
- 2018
- Publisher :
- John Wiley and Sons Inc., 2018.
-
Abstract
- In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells.
- Subjects :
- 0301 basic medicine
Transcriptional Activation
Cancer Research
Hot Temperature
Nerve Tissue Proteins
HSF1
03 medical and health sciences
Mice
0302 clinical medicine
Side population
SOX2
Cell, Molecular, and Stem Cell Biology
Heat Shock Transcription Factors
cellular stress
Stress, Physiological
Heat shock protein
Cell Line, Tumor
Animals
Humans
Phosphorylation
Transcription factor
Side-Population Cells
PI3K/AKT/mTOR pathway
Gene knockdown
Chemistry
SOXB1 Transcription Factors
kidney cancer
General Medicine
Original Articles
HSP40 Heat-Shock Proteins
cancer stem‐like cell
Kidney Neoplasms
Cell biology
Heat shock factor
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Neoplastic Stem Cells
DNAJB8
Original Article
Neoplasm Transplantation
Molecular Chaperones
Subjects
Details
- Language :
- English
- ISSN :
- 13497006 and 13479032
- Volume :
- 109
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....826ed31b88e8a1432040a52a40eeae77