HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer

Wang, Weiguo; Jiang, Xinjie; Xia, Fei; Chen, Xudong; Li, Guojun; Liu, Lizhuan; Xu, Qiang; Zhu, Min; Cheng, Chen

doi:10.1007/s11033-022-07978-x

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…Recent studies have also implicated GRP170 in tumorigenesis associated with several cancers, including bladder, papillary thyroid, and breast. Of note, overexpression of GRP170 correlates with poor outcomes, increased cell mobility, and proliferation (Wang et al, 2023), (Wang et al, 2021), (Lee et al, 2021), (Hao et al, 2021). In addition, a requirement for GRP170 NEF activity in both cholera toxin and polyomavirus pathogenesis was uncovered, since GRP170 releases BiP from the toxin/virus, which is needed for ER to the cytosol retrotranlsocation and pathogenesis (Inoue and Tsai, 2015), (Williams et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also implicated GRP170 in tumorigenesis associated with several cancers, including bladder, papillary thyroid, and breast. Of note, overexpression of GRP170 correlates with poor outcomes, increased cell mobility, and proliferation (Wang et al, 2023), (Wang et al, 2021), (Lee et al, 2021), (Hao et al, 2021). In addition, a requirement for GRP170 NEF activity in both (which was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

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Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Mann,

Melendez-Suchi,

Sukhoplyasova

et al. 2023

Preprint

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GRP170, a product of the Hyou1 gene, is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of embryonic fibroblasts from mice in which LoxP sites were engineered in the Hyou1 loci (Hyou1LoxP/LoxP). A doxycycline-regulated Cre recombinase was also stably introduced into these cells. Induction of Cre resulted in excision of Hyou1 and depletion of Grp170 protein, culminating in apoptotic cell death. As Grp170 levels fell we observed increased steady-state binding of BiP to a client, slowed degradation of a misfolded BiP substrate, and BiP accumulation in NP40-insoluble fractions. Consistent with disrupted BiP functions, we observed reactivation of BiP storage pools and induction of the unfolded protein response (UPR) in futile attempts to provide compensatory increases in ER chaperones and folding enzymes. Together, these results provide insights into the cellular consequences of controlled Grp170 loss and insights into mutations in the Hyou1 locus and human disease.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies have also implicated GRP170 in tumorigenesis associated with several cancers, including bladder, papillary thyroid, and breast. Of note, overexpression of GRP170 correlates with poor outcomes, increased cell mobility, and proliferation (Wang et al, 2023), (Wang et al, 2021), (Lee et al, 2021), (Hao et al, 2021). In addition, a requirement for GRP170 NEF activity in both (which was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Mann,

Melendez-Suchi,

Sukhoplyasova

et al. 2023

Preprint

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“…Second, ATF6 activation resulted in BiP up-regulation ( Yoshida et al. , 1998 ; Wang et al. , 2000 ).…”

Section: Resultsmentioning

confidence: 99%

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function

Mann,

Melendez-Suchi,

Vorndran

et al. 2024

MBoC

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GRP170 ( Hyou1) is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of mouse embryonic fibroblasts obtained from mice in which LoxP sites were engineered in the Hyou1 loci ( Hyou1LoxP/LoxP). A doxycycline-regulated Cre recombinase was stably introduced into these cells. Induction of Cre resulted in depletion of Grp170 protein which culminated in cell death. As Grp170 levels fell we observed a portion of BiP fractionating with insoluble material, increased binding of BiP to a client with a concomitant reduction in its turnover, and reduced solubility of an aggregation-prone BiP substrate. Consistent with disrupted BiP functions, we observed reactivation of BiP and induction of the unfolded protein response (UPR) in futile attempts to provide compensatory increases in ER chaperones and folding enzymes. Together, these results provide insights into the cellular consequences of controlled Grp170 loss and provide hypotheses as to why mutations in the Hyou1 locus are linked to human disease.

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“…Additionally, SUGT1 can activate the NOD-like receptor family to eliminate damaged proteins, thereby counteracting the negative impacts of high-temperature stress ( da Silva Correia et al, 2007 ; Hong and Hahn, 2016 ). The expression product of the HYOU1 gene can activate the PI3K-AKT signaling pathway to promote cell growth and migration ( Li et al, 2019 ; Wang et al, 2022 ). Such genes were all significantly downregulated, indicating that excessive temperature would destroy the anti-stress system of S. esculenta larvae and reduce the expression of proteins.…”

Section: Discussionmentioning

confidence: 99%

Exploration of anti-stress mechanisms in high temperature exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling

Wang

Bao

et al. 2023

Front. Physiol.

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Sepia esculenta is a cephalopod widely distributed in the Western Pacific Ocean, and there has been growing research interest due to its high economic and nutritional value. The limited anti-stress capacity of larvae renders challenges for their adaptation to high ambient temperatures. Exposure to high temperatures produces intense stress responses, thereby affecting survival, metabolism, immunity, and other life activities. Notably, the molecular mechanisms by which larval cuttlefish cope with high temperatures are not well understood. As such, in the present study, transcriptome sequencing of S. esculenta larvae was performed and 1,927 differentially expressed genes (DEGs) were identified. DEGs were subjected to functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The top 20 terms of biological processes in GO and 20 high-temperature stress-related pathways in KEGG functional enrichment analysis were identified. A protein-protein interaction network was constructed to investigate the interaction between temperature stress-related genes. A total of 30 key genes with a high degree of participation in KEGG signaling pathways or protein-protein interactions were identified and subsequently validated using quantitative RT-PCR. Through a comprehensive analysis of the protein-protein interaction network and KEGG signaling pathway, the functions of three hub genes (HSP90AA1, PSMD6, and PSMA5), which belong to the heat shock protein family and proteasome, were explored. The present results can facilitate further understanding of the mechanism of high temperature resistance in invertebrates and provide a reference for the S. esculenta industry in the context of global warming.

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HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer

Cited by 5 publications

References 30 publications

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function

Exploration of anti-stress mechanisms in high temperature exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling

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