Lemur tyrosine kinase 2 (LMTK2) is a determinant of cell sensitivity to apoptosis by regulating the levels of the BCL2 family members

Conti, Annalisa; Majorini, Maria Teresa; Fontanella, Enrico; Bardelli, Alberto; Giacca, Mauro; Delia, Domenico; Mano, Miguel; Lecis, Daniele

doi:10.1016/j.canlet.2016.12.025

Cited by 25 publications

(31 citation statements)

References 38 publications

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“…The apoptotic gene controls cell survival and does not affect cell proliferation. 22 The antiapoptotic mechanisms of Bcl-2 include inhibition of ion channel opening that is activated by IP3R, which thereby inhibits the release of Ca2 + from the endoplasmic reticulum and produces antiapoptotic effect. 23 The coexpression of Bcl-2 and P53 genes could delay the role of P53 gene-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Yang

Chen

Wang

et al. 2017

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Glioma is one of the most common types of adult primary brain tumors, and the underlying molecular mechanisms still remain unclear. Nuclear factor-kappa B1 (NF-κB1) is involved in a variety of malignancies and is widely expressed in malignant tumors. However, the expression of NF-κB1 in different grades of glioma, the correlation between NF-κB1 and Bcl-2 expressions in gliomas, and the research between NF-κB1 and early apoptosis of glioma cells have not been reported so far. In this study, the expression level of NF-κB1 in 31 human glioma tissues and six nonneoplastic brain tissues was determined using quantitative real-time polymerase chain reaction. Results showed that the expression of NF-κB1 in human glioma tissues and glioma cell lines, SHG44 and U87, was significantly higher compared to noncancerous brain tissues and that the expression increased with increasing degrees of tumor malignancy. Similar results were demonstrated with the expression of Bcl-2 in the same human glioma specimens. Flow cytometry results showed that inhibition of NF-κB1 expression significantly promoted apoptosis of SHG44 and U87 in human glioma cells. Western blot analysis further confirmed decreased expression of Bcl-2 protein after inhibition of NF-κB1 protein expression. Taken together, NF-κB1 overexpression inhibits early apoptosis of glioma cells and high expression of NF-κB1 promotes the expression of antiapoptotic gene Bcl-2. Therefore, our study results provide a theoretical basis for antiapoptotic mechanism of tumor cells in association with NF-κB1.

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Section: Discussionmentioning

confidence: 99%

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Yang

Chen

Wang

et al. 2017

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“…Note that SM130 requires a longer time of incubation in order to establish a covalent bond and induce a stabilizing effect. EC 50 Remarkably, the strong reduction of PARP cleavage, which is detected in cells treated with SM130 and depleted for caspase-8 ( Fig. 5A left panel), suggests that SM130 mainly activates the extrinsic apoptotic pathway.…”

Section: Sm130 Induces Apoptosis In Mda-mb231 Cancer Cells More Efficmentioning

confidence: 87%

“…Cells were transiently knocked down following a reverse transfection protocol employing siRNAs (Dharmacon) and RNAiMAX reagent (Thermo Fisher Scientific, Rodano, Italy) as already reported [50].…”

Section: Transfectionmentioning

confidence: 99%

Structure‐based design and molecular profiling of Smac‐mimetics selective for cellular IAPs

et al. 2018

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“…Further studies are needed to reveal the functions of ALPL in AML. Lemur tyrosine kinase 2 (LMTK2) is a tumor suppressor that is downregulated in some neurodegenerative diseases (28) and can inhibit the activity of PP1C by controlling GSK3β phosphorylation (29). The effect of LMTK2 on the pathogenesis of AML has not been studied, but LMTK2 is predicted to enhance the cytotoxic activity of natural killer cells to kill leukemic blast cells via inhibition of GSK3β (30).…”

Section: Discussionmentioning

confidence: 99%

Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

et al. 2020

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Acute myeloid leukemia (AML) is a hematological malignancy with a poorly understood pathogenesis, especially among patients with no known cytogenetic abnormalities. Furthermore, there is a lack of therapeutic gene targets and diagnostic biomarkers for the effective treatment of AML. The present study aimed to identify candidate biomarkers correlated with the clinical prognosis of patients with AML. Leukemic cells from 5 patients with AML exhibiting a normal karyotype, and hematopoietic cells from 5 healthy donors were processed for RNA sequencing (RNA-seq), and the obtained RNA expression profiles were subjected to weighted gene correlation network analysis. A novel group of genes (the red module) were identified to be significantly associated with AML, and this module contained a closely connected network with 147 nodes, which corresponded to 114 mRNAs. Analysis of the correlation between these mRNAs and blast cell percentage, overall survival (OS) and disease-free survival (DFS) using cases from The Cancer Genome Atlas (TCGA) database revealed that CSF3R, ALPL and LMTK2 were negatively associated with the percentage of blast cells, while high expression of these genes was associated with longer OS and DFS in patients with AML. The differential expression of these three genes between patients with AML and healthy control subjects was supported using the Genotype-Tissue Expression and TCGA databases and was further confirmed using reverse transcription-quantitative (RT-qPCR). These genes exhibited significantly lower expression in patients with AML compared with control subjects. The results indicated that CSF3R, ALPL and LMTK2 exhibit the potential to be prognostic biomarkers. However, the biological functions of these three candidate genes need to be assessed in further studies.

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Lemur tyrosine kinase 2 (LMTK2) is a determinant of cell sensitivity to apoptosis by regulating the levels of the BCL2 family members

Cited by 25 publications

References 38 publications

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Structure‐based design and molecular profiling of Smac‐mimetics selective for cellular IAPs

Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

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