ArticleBlood2012
Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.Molecular oncology · 2025Article
- Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cancer-Targeting Peptides Functionalized With Polyarginine Enables GRP78-Dependent Cell Uptake and siRNA Delivery Within the DU145 Prostate Cancer Cells.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Targeting GRP78 suppresses oncogenic KRAS protein expression and reduces viability of cancer cells bearing various KRAS mutations.Neoplasia (New York, N.Y.) · 2022Article
- Article
- Evidence for Recombinant GRP78, CALR, PDIA3 and GPI as Mediators of Genetic Instability in Human CD34+ Cells.Cancers · 2022Article
- Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics.Scientific reports · 2022Article
- CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells.Nature communications · 2022Article
- Article
- Suppression of ER-stress induction of GRP78 as an anti-neoplastic mechanism of the cardiac glycoside Lanatoside C in pancreatic cancer: Lanatoside C suppresses GRP78 stress induction.Neoplasia (New York, N.Y.) · 2021Article
- Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells.International journal of molecular sciences · 2021Article
- Article
- Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells.Blood advances · 2020Article
- Review
- Targeting Translation Activity at the Ribosome Interface with UV-Active Small Molecules.ACS omega · 2019Article
- ATF6α Activation Enhances Survival against Chemotherapy and Serves as a Prognostic Indicator in Osteosarcoma.Neoplasia (New York, N.Y.) · 2019Article
- GRP78 regulates milk biosynthesis and the proliferation of bovinemammaryepithelial cells through the mTOR signaling pathway.Cellular & molecular biology letters · 2019Article
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Traditionally, GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors; thus, its role in the development of hematologic malignancies remains to be determined. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null BM cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first demonstration that GRP78 is a critical effector of leukemia progression, at least in part through regulation of oncogenic PI3K/AKT signaling. In agreement with PI3K/AKT as an effector for cytosine arabinoside resistance in acute myeloid leukemia, overexpression of GRP78 renders human leukemic cells more resistant to cytosine arabinoside-induced apoptosis, whereas knockdown of GRP78 sensitizes them. These, coupled with the emerging association of elevated GRP78 expression in leukemic blasts of adult patients and early relapse in childhood leukemia, suggest that GRP78 is a novel therapeutic target for leukemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.