ArticleBlood2009
Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
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- Porcine Epidemic Diarrhea Virus and Its nsp14 Suppress ER Stress Induced GRP78.International journal of molecular sciences · 2023Article
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- Roles and Regulation of BCL-xL in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Anticancer Effect of Polyphyllin I in Suppressing Stem Cell-Like Properties of Hepatocellular Carcinoma via the AKT/GSK-3Oxidative medicine and cellular longevity · 2022Article
- Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.Mediators of inflammation · 2021Review
- Anti-proliferative, pro-apoptotic and anti-invasive effect of the copper coordination compound Cas III-La through the induction of reactive oxygen species and regulation of Wnt/β-catenin pathway in glioma.Journal of Cancer · 2021Article
- Review
- Cancer cell specific inhibition of Wnt/β-catenin signaling by forced intracellular acidification.Cell discovery · 2018Article
- Regulation of the Endoplasmic Reticulum Stress by BIP/GRP78 is involved in Meiotic Maturation of Porcine OocytesDevelopment & reproduction · 2017Article
- Review
- A Wnt Pathway Activator Induces Apoptosis and Cell Death in Mouse Monocytic Leukemia Cells.Oncology research · 2017Article
- Apoptosis by [Pt(O,O'-acac)(γ-acac)(DMS)] requires PKC-δ mediated p53 activation in malignant pleural mesothelioma.PloS one · 2017Article
- Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression.Oncogene · 2015Review
- Targeting phospho-MARCKS overcomes drug-resistance and induces antitumor activity in preclinical models of multiple myeloma.Leukemia · 2015Article
- Preclinical efficacy of sepantronium bromide (YM155) in multiple myeloma is conferred by down regulation of Mcl-1.Oncotarget · 2014Article
- Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.International journal of molecular sciences · 2014Article
- Role of protein kinase C in podocytes and development of glomerular damage in diabetic nephropathy.Frontiers in endocrinology · 2014Review
- FTY720 induces apoptosis in B16F10-NEX2 murine melanoma cells, limits metastatic development in vivo, and modulates the immune system.Clinics (Sao Paulo, Brazil) · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Targeting protein kinase C (PKC) isoforms by the small molecule inhibitor enzastaurin has shown promising preclinical activity in a wide range of tumor cells. We further delineated its mechanism of action in multiple myeloma (MM) cells and found a novel role of beta-catenin in regulating growth and survival of tumor cells. Specifically, inhibition of PKC leads to rapid accumulation of beta-catenin by preventing the phosphorylation required for its proteasomal degradation. Microarray analysis and small-interfering RNA (siRNA)-mediated gene silencing in MM cells revealed that accumulated beta-catenin activates early endoplasmic reticulum stress signaling via eIF2alpha, C/EBP-homologous protein (CHOP), and p21, leading to immediate growth inhibition. Furthermore, accumulated beta-catenin contributes to enzastaurin-induced cell death. Sequential knockdown of beta-catenin, c-Jun, and p73, as well as overexpression of beta-catenin or p73 confirmed that accumulated beta-catenin triggers c-Jun-dependent induction of p73, thereby conferring MM cell apoptosis. Our data reveal a novel role of beta-catenin in endoplasmic reticulum (ER) stress-mediated growth inhibition and a new proapoptotic mechanism triggered by beta-catenin on inhibition of PKC isoforms. Moreover, we identify p73 as a potential novel therapeutic target in MM. Based on these and previous data, enzastaurin is currently under clinical investigation in a variety of hematologic malignancies, including MM.
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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.