%0 Journal Article
%A Kwon, Yujin
%A Kim, Jiyoon
%A Cho, Su-Yeon
%A Kang, Yoon Jin
%A Lee, Jongsoo
%A Kwon, Jaeyoung
%A Rhee, Hyungjin
%A Bauer, Sebastian
%A Kim, Hyung-Sik
%A Lee, Esak
%A Kim, Han Sang
%A Jung, Jae Hung
%A Kim, Hoguen
%A Kim, Won Kyu
%T Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT.
%J Cell death and differentiation
%V 30
%N 10
%@ 1350-9047
%C London
%I Macmillan
%M DKFZ-2023-01874
%P 2309-2321
%D 2023
%Z 2023 Oct;30(10):2309-2321
%X 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
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37704840
%R 10.1038/s41418-023-01220-2
%U https://inrepo02.dkfz.de/record/282755