PMID- 29316077 OWN - NLM STAT- MEDLINE DCOM- 20180312 LR - 20210109 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 109 IP - 3 DP - 2018 Mar TI - Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1. PG - 741-750 LID - 10.1111/cas.13501 [doi] AB - 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. CI - (c) 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Kusumoto, Hiroki AU - Kusumoto H AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Urology, Wakayama Medical University, Wakayama, Japan. FAU - Hirohashi, Yoshihiko AU - Hirohashi Y AUID- ORCID: 0000-0002-0608-3914 AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Nishizawa, Satoshi AU - Nishizawa S AUID- ORCID: 0000-0002-1475-6381 AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Urology, Wakayama Medical University, Wakayama, Japan. FAU - Yamashita, Masamichi AU - Yamashita M AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Yasuda, Kazuyo AU - Yasuda K AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Murai, Aiko AU - Murai A AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Takaya, Akari AU - Takaya A AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Mori, Takashi AU - Mori T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Urology, Wakayama Medical University, Wakayama, Japan. FAU - Kubo, Terufumi AU - Kubo T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Nakatsugawa, Munehide AU - Nakatsugawa M AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kanaseki, Takayuki AU - Kanaseki T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Tsukahara, Tomohide AU - Tsukahara T AUID- ORCID: 0000-0002-3678-4359 AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kondo, Toru AU - Kondo T AD - Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. FAU - Sato, Noriyuki AU - Sato N AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Hara, Isao AU - Hara I AUID- ORCID: 0000-0003-4542-4045 AD - Department of Urology, Wakayama Medical University, Wakayama, Japan. FAU - Torigoe, Toshihiko AU - Torigoe T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. LA - eng PT - Journal Article DEP - 20180220 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (DNAJB8 protein, human) RN - 0 (HSF1 protein, human) RN - 0 (HSP40 Heat-Shock Proteins) RN - 0 (Heat Shock Transcription Factors) RN - 0 (Molecular Chaperones) RN - 0 (Nerve Tissue Proteins) RN - 0 (SOX2 protein, human) RN - 0 (SOXB1 Transcription Factors) SB - IM MH - Animals MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic MH - HSP40 Heat-Shock Proteins/genetics/*metabolism MH - Heat Shock Transcription Factors/genetics/*metabolism MH - Hot Temperature MH - Humans MH - Kidney Neoplasms/genetics/*metabolism MH - Mice MH - Molecular Chaperones/genetics/*metabolism MH - Neoplasm Transplantation MH - Neoplastic Stem Cells/*cytology/metabolism MH - Nerve Tissue Proteins/genetics/*metabolism MH - Phosphorylation MH - SOXB1 Transcription Factors/genetics/*metabolism MH - Side-Population Cells/cytology/metabolism MH - Stress, Physiological MH - Transcriptional Activation PMC - PMC5834799 OTO - NOTNLM OT - DNAJB8 OT - HSF1 OT - cancer stem-like cell OT - cellular stress OT - kidney cancer EDAT- 2018/01/10 06:00 MHDA- 2018/03/13 06:00 PMCR- 2018/03/01 CRDT- 2018/01/10 06:00 PHST- 2017/09/27 00:00 [received] PHST- 2017/12/22 00:00 [revised] PHST- 2017/12/30 00:00 [accepted] PHST- 2018/01/10 06:00 [pubmed] PHST- 2018/03/13 06:00 [medline] PHST- 2018/01/10 06:00 [entrez] PHST- 2018/03/01 00:00 [pmc-release] AID - CAS13501 [pii] AID - 10.1111/cas.13501 [doi] PST - ppublish SO - Cancer Sci. 2018 Mar;109(3):741-750. doi: 10.1111/cas.13501. Epub 2018 Feb 20.