ArticleCell death & disease2014
APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
The trial behind it
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication.Virulence · 2022Article
- Involvement of adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 in diallyl trisulfide-induced cytotoxicity in hepatocellular carcinoma cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures.Cancers · 2020Article
- APPL2 Negatively Regulates Olfactory Functions by Switching Fate Commitments of Neural Stem Cells in Adult Olfactory Bulb via Interaction with Notch1 Signaling.Neuroscience bulletin · 2020Article
- ATM Expression Is Elevated in Established Radiation-Resistant Breast Cancer Cells and Improves DNA Repair Efficiency.International journal of biological sciences · 2020Article
- Transcriptome analysis of differentially expressed genes and pathways associated with mitoxantrone treatment prostate cancer.Journal of cellular and molecular medicine · 2019Article
- Adaptor Protein APPL2 Affects Adult Antidepressant Behaviors and Hippocampal Neurogenesis via Regulating the Sensitivity of Glucocorticoid Receptor.Molecular neurobiology · 2018Article
- ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.Scientific reports · 2017Article
- Susceptibility of ATM-deficient pancreatic cancer cells to radiation.Cell cycle (Georgetown, Tex.) · 2017Article
- Appl1 and Appl2 are Expendable for Mouse Development But Are Essential for HGF-Induced Akt Activation and Migration in Mouse Embryonic Fibroblasts.Journal of cellular physiology · 2016Article
- Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Expression of APPL1 is correlated with clinicopathologic characteristics and poor prognosis in patients with gastric cancer.Current oncology (Toronto, Ont.) · 2016Article
- APPL1-Mediating Leptin Signaling Contributes to Proliferation and Migration of Cancer Cells.PloS one · 2016Article
- ILKAP, ILK and PINCH1 control cell survival of p53-wildtype glioblastoma cells after irradiation.Oncotarget · 2015Article
- Screening of Long Noncoding RNAs Induced by Radiation Using Microarray.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite intensive multimodal therapies, the overall survival rate of patients with ductal adenocarcinoma of the pancreas is still poor. The chemo- and radioresistance mechanisms of this tumor entity remain to be determined in order to develop novel treatment strategies. In cancer, endocytosis and membrane trafficking proteins are known to be utilized and they also critically regulate essential cell functions like survival and proliferation. On the basis of these data, we evaluated the role of the endosomal proteins adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif (APPL)1 and 2 for the radioresistance of pancreatic carcinoma cells. Here, we show that APPL2 expression in pancreatic cancer cells is upregulated after irradiation and that depletion of APPL proteins by small interfering RNA (siRNA) significantly reduced radiation survival in parallel to impairing DNA double strand break (DSB) repair. In addition, APPL knockdown diminished radiogenic hyperphosphorylation of ataxia telangiectasia mutated (ATM). Activated ATM and APPL1 were also shown to interact after irradiation, suggesting that APPL has a more direct role in the phosphorylation of ATM. Double targeting of APPL proteins and ATM caused similar radiosensitization and concomitant DSB repair perturbation to that observed after depletion of single proteins, indicating that ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair. These data strongly suggest that endosomal APPL proteins contribute to the DNA damage response. Whether targeting of APPL proteins is beneficial for the survival of patients with pancreatic adenocarcinoma remains to be elucidated.
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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.