TY  - JOUR
AU  - Kwon, Yujin
AU  - Kim, Jiyoon
AU  - Cho, Su-Yeon
AU  - Kang, Yoon Jin
AU  - Lee, Jongsoo
AU  - Kwon, Jaeyoung
AU  - Rhee, Hyungjin
AU  - Bauer, Sebastian
AU  - Kim, Hyung-Sik
AU  - Lee, Esak
AU  - Kim, Han Sang
AU  - Jung, Jae Hung
AU  - Kim, Hoguen
AU  - Kim, Won Kyu
TI  - Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT.
JO  - Cell death and differentiation
VL  - 30
IS  - 10
SN  - 1350-9047
CY  - London
PB  - Macmillan
M1  - DKFZ-2023-01874
SP  - 2309-2321
PY  - 2023
N1  - 2023 Oct;30(10):2309-2321
AB  - Gastrointestinal stromal tumors (GISTs) frequently show KIT mutations, accompanied by overexpression and aberrant localization of mutant KIT (MT-KIT). As previously established by multiple studies, including ours, we confirmed that MT-KIT initiates downstream signaling in the Golgi complex. Basic leucine zipper nuclear factor 1 (BLZF1) was identified as a novel MT-KIT-binding partner that tethers MT-KIT to the Golgi complex. Sustained activation of activated transcription factor 6 (ATF6), which belongs to the unfolded protein response (UPR) family, alleviates endoplasmic reticulum (ER) stress by upregulating chaperone expression, including heat shock protein 90 (HSP90), which assists in MT-KIT folding. BLZF1 knockdown and ATF6 inhibition suppressed both imatinib-sensitive and -resistant GIST in vitro. ATF6 inhibitors further showed potent antitumor effects in GIST xenografts, and the effect was enhanced with ER stress-inducing drugs. ATF6 activation was frequently observed in 67
LB  - PUB:(DE-HGF)16
C6  - pmid:37704840
DO  - DOI:10.1038/s41418-023-01220-2
UR  - https://inrepo02.dkfz.de/record/282755
ER  -