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dc.contributor.authorLiu, H.
dc.contributor.authorXie, S.
dc.contributor.authorKalvakolanu, D.V.
dc.date.accessioned2020-06-24T20:50:59Z
dc.date.available2020-06-24T20:50:59Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086324502&doi=10.1038%2fs41419-020-2656-0&partnerID=40&md5=a95472e994c9729f727eed677f8e00cd
dc.identifier.urihttp://hdl.handle.net/10713/13135
dc.description.abstractSHQ1 was reported to control the biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). It was independently isolated as a growth suppressor, GRIM1, in a genetic screen. Recent studies have indicated that SHQ1 inhibits prostate cancer growth and metastasis. SHQ1 facilitates MYC RNA splicing to promote T-acute lymphoblastic leukemia (T-ALL) development. Thus, the mechanisms of SHQ1 in cancers remain largely unknown. We report here that SHQ1 promotes tumor apoptosis and chemo-sensitivity in hepatocellular carcinoma (HCC) cells. In HCC tissues from patients, expression of SHQ1 was significantly decreased in the tumor compared to adjacent tissues. Experiments with HCC xenograft models revealed that restoring SHQ1 levels enhanced the anti-tumor activity of the endoplasmic reticulum (ER) stress inducer tunicamycin (TM) and common chemotherapy drug paclitaxel (PTX). Mechanistically, SHQ1 is an ER-stress response gene which is regulated by p50ATF6 and XBP1s through an ER stress response like element located on the SHQ1 promoter. SHQ1 interacts with the ER chaperone GRP78 to release ER sensors PERK/IRE1α/ATF6 from GRP78/ER-sensor complexes, leading to hyper-activation of unfolded protein response (UPR). In the persistent ER stress conditions of a HepG2 xenograft tumor model, SHQ1-mediated hyper-activation of ER-sensor signaling induces apoptosis. Our study thus demonstrates a SHQ1-mediated ER-stress response feedback loop that promotes tumor sensitivity to chemotherapeutics. Copyright 2020, The Author(s).en_US
dc.description.sponsorshipThis work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB29030000), the Ministry of Science and Technology of China (Grant No. 2016YFC1303503), the National Natural Science Foundation of China (Grant Nos. 81671558, 81302521, and 31571440) and the Fundamental Research Funds for the Central Universities (Grant No. YD2070002004).en_US
dc.description.urihttps://doi.org/10.1038/s41419-020-2656-0en_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofCell Death and Disease
dc.subjectSHQ1
dc.subjecttumor apoptosisen_US
dc.subjectchemo-sensitivityen_US
dc.subject.meshCarcinoma, Hepatocellularen_US
dc.titleSHQ1 is an ER stress response gene that facilitates chemotherapeutics-induced apoptosis via sensitizing ER-stress responseen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41419-020-2656-0
dc.identifier.pmid32522979


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