Open AccessCellular stress induces cancer stem‐like cells through expression of DNAJB 8 by activation of heat shock factor 1
Author(s) -
Kusumoto Hiroki,
Hirohashi Yoshihiko,
Nishizawa Satoshi,
Yamashita Masamichi,
Yasuda Kazuyo,
Murai Aiko,
Takaya Akari,
Mori Takashi,
Kubo Terufumi,
Nakatsugawa Munehide,
Kanaseki Takayuki,
Tsukahara Tomohide,
Kondo Toru,
Sato Noriyuki,
Hara Isao,
Torigoe Toshihiko
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13501
Subject(s) - gene knockdown , heat shock factor , heat shock , heat shock protein , hsf1 , biology , stem cell , cancer cell , western blot , pi3k/akt/mtor pathway , transcription factor , microbiology and biotechnology , cancer research , chemistry , cell culture , hsp70 , gene , cancer , signal transduction , genetics
In a previous study, we found that DNAJB 8, 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 DNAJB 8 and SOX 2. Gene knockdown experiments using si RNA s showed that the increase in SOX 2 expression and SP cell ratio depends on DNAJB 8 and that the increase in DNAJB 8 and SOX 2 depend on HSF 1. Furthermore, treatment with a mammalian target of rapamycin ( mTOR ) inhibitor, temsirolimus, decreased the expression of DNAJB 8 and SOX 2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB 8 by activation of HSF 1 and induces cancer stem‐like cells.