Amyloid β protein precursor is involved in the growth of human colon carcinoma cellin vitro andin vivo

Jingyan, Meng; Kataoka, Hiroaki; Itoh, Hiroshi; Koono, Masashi

doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1155>3.0.co;2-h

Cited by 63 publications

(20 citation statements)

References 31 publications

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“…Interestingly, APP is increased in many different cancers, such as colon cancer, pancreatic cancer, and thyroid cancer 29–31. Lim et al32 found that overexpression of APP is found both in malignant breast cancer cell lines and in human breast cancer tissues, and APP could regulate cell growth, apoptosis, and motility of breast cancer, possibly via engagement of AKT-mediated signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

Identification of potential biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma by bioinformatics analysis

Yang

Chen

Huang

et al. 2017

OTT

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The purpose of this study was to find disease-associated genes and potential mechanisms in head and neck squamous cell carcinoma (HNSCC) with deoxyribonucleic acid microarrays. The gene expression profiles of GSE6791 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were obtained with packages in R language and STRING constructed protein–protein interaction (PPI) network of the DEGs with combined score >0.8. Subsequently, module analysis of the PPI network was performed by Molecular Complex Detection plugin and functions and pathways of the hub gene in subnetwork were studied. Finally, overall survival analysis of hub genes was verified in TCGA HNSCC cohort. A total of 811 DEGs were obtained, which were mainly enriched in the terms related to extracellular matrix (ECM)–receptor interaction, ECM structural constituent, and ECM organization. A PPI network was constructed, consisting of 401 nodes and 1,254 edges and 15 hub genes with high degrees in the network. High expression of 4 genes of the 15 genes was associated with poor OS of patients in HNSCC, including PSMA7, ITGA6, ITGB4, and APP. Two significant modules were detected from the PPI network, and the enriched functions and pathways included proteasome, ECM organization, and ECM–receptor interaction. In conclusion, we propose that PSMA7, ITGA6, ITGB4, and APP may be further explored as potential biomarkers to aid HNSCC diagnosis and treatment.

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Section: Resultsmentioning

confidence: 99%

Identification of potential biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma by bioinformatics analysis

Yang

Chen

Huang

et al. 2017

OTT

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“…More recently, APP has been shown to play a role in cancer. Expression of the protein stimulates colon carcinoma cell proliferation [3] and an increase in APP mRNA expression in oral squamous cell carcinomas is associated with a reduction in patient survival [4] . Thyroid cancers are characterised by up regulation of APP protein and mRNA expression [5] with the former also being enhanced in pancreatic cancer tissue specimens [6] .…”

Section: Introductionmentioning

confidence: 99%

The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

Gough

Blanthorn-Hazell

Delury

et al. 2014

Biochemical and Biophysical Research Communications

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“…A variety of cell cycle regulatory proteins, including proliferating cell nuclear antigen, cyclin D1, Cdk4, and cyclin B1, have been detected in animal models of AD well before the presence of plaques, and in human brain regions that display AD pathology [15–17]. Interestingly, APP processing is also elevated in tumors, pancreatic cancer, oral squamous cell carcinomas and colon carcinomas, which collectively imply that APP catabolism is linked to mechanisms involved in cellular proliferation [18–20]. Though the degree of APP processing is clearly altered in both neuronal and oncogenic signaling pathways, the relevance of neuronal cell cycle re-entry to AD pathogenesis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1

Myre

Washicosky

Moir

et al. 2009

Cellular Signalling

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The detection of cell cycle proteins in Alzheimer’s disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Aβ properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid β-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Aβ40 and Aβ42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Aβ42 to Aβ40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Aβ. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a γ-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668.

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Amyloid β protein precursor is involved in the growth of human colon carcinoma cellin vitro andin vivo

Cited by 63 publications

References 31 publications

Identification of potential biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma by bioinformatics analysis

Identification of potential biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma by bioinformatics analysis

The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1

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