Akt/mTOR mediated induction of bystander effect signaling in a nucleus independent manner in irradiated human lung adenocarcinoma epithelial cells

Li, Lü; Wang, Lu; Prise, Kevin M.; Yu, K.N.; Chen, Guodong; Chen, Lianyun; Han, Wei

doi:10.18632/oncotarget.14931

Cited by 11 publications

(6 citation statements)

References 42 publications

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“…In the present study, the expression of phosphorylated p38, JNK, ERK1/2, and P65 proteins were increased in bystander effect cells treated with conditioned medium only at 6 h, which indicates that the MAPK/NF-κB pathway is activated in bystander cells at this time. This result is consistent with other reports [ 37 , 38 , 46 ]. After treatment with APS, p-ERK/ERK, p-P38/P38, and p-NF-κB/NF-κB fold change was decreased.…”

Section: Discussionsupporting

confidence: 94%

“…This indicates that cell growth slows and the genomic instability is enhanced in bystander cells after treatment with conditioned medium. This is accordance with others studies [ 37 , 38 ]. In the present study, APS had protective effects on cell survival level of bystander cells against conditioned medium and maintained the stability of the genome through decreasing 53BP1 foci number and MN formation.…”

Section: Discussionsupporting

confidence: 94%

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Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs)

et al. 2018

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BackgroundThis study investigated the effect of Astragalus polysaccharides (APS) on radiation-induced bystander effects (RIBE) in human bone mesenchymal stem cells (BMSCs) induced by irradiated A549 cells.Material/MethodsA549 cells were irradiated with 2 Gy X-rays to obtain conditioned medium. BMSCs were incubated with the conditioned medium or APS. The levels of reactive oxygen species (ROS) and TGF-β were detected by ELISA. Cell survival, genomic instability, and DNA damages were detected by CCK-8 assay, colony formation assay, the micronucleus test and immunofluorescence assay, respectively. The protein and phosphorylation protein expression of p38, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK1/2), P65, and cyclooxygenase-2 (COX-2) in bystander effect cells were detected by Western blot.ResultsThe expression of COX-2 and ROS increased following stimulation with conditioned medium; this effect was inhibited by pre-exposing the cells to APS. BMSCs growth and colony formation rate decreased following stimulation with conditioned medium; this effect was suppressed by pre-exposing the cells to APS. In addition, the micronucleus rate and 53BP1 foci number increased after treatment with conditioned medium; this increase in BMSCs was inhibited by APS. The levels of phosphorylated p38, JNK, ERK1/2, NF-κB P65, and COX-2 proteins were increased by conditioned medium but were decreased by pre-treatment with APS.ConclusionsRIBE in BMSCs induced by the irradiated A549 was mediated by the ROS in the conditioned medium and might be related to MAPK/NF-κB signal pathways in BMSCs. APS may block RIBE through regulating the MAPK/NF-κB pathway.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs)

et al. 2018

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“…In controlling cell survival, differentiation and malignant transformation, the AKT/mTOR pathway is one of the main pathways . Suppression of this pathway is considered a latent antitumor therapy . The Akt/mTOR pathway is a critical pathway for LUAD cell proliferation .…”

Section: Discussionmentioning

confidence: 99%

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

et al. 2020

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Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5‐year relative survival rate is no more than 1%. Dysregulation of components of striatin‐interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin‐interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT‐PCR (qRT‐PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC‐A1 cells and depleted STRIP2 in Calu‐3 cells. Cell proliferation was evaluated by Cell Counting Kit‐8 and colony‐forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu‐3 cells, and overexpression of STRIP2 had the opposite effects in SPC‐A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p‐Akt and phosphorylated‐mammalian target of rapamycin (p‐mTOR) in Calu‐3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC‐A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E‐cadherin and reduced levels of N‐cadherin, Vimentin and matrix metalloproteinase‐9 in Calu‐3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC‐A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial–mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.

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“…Tumor cells are very sensitive to CDDP, but they begin to develop drug resistance with chemotherapy [23]. This is an important reason for failures in clinical treatment of malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery combined with chemotherapy is one of the major methods for clinical treatment of NSCLC, and cisplatin is one of the most common drugs for chemotherapy after tumor surgery [ 22 ]. Tumor cells are very sensitive to CDDP, but they begin to develop drug resistance with chemotherapy [ 23 ]. This is an important reason for failures in clinical treatment of malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

CLDN1 Increases Drug Resistance of Non-Small Cell Lung Cancer by Activating Autophagy via Up-Regulation of ULK1 Phosphorylation

Zhao

Jiang

et al. 2017

Med Sci Monit

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BackgroundThe aim of this study was to investigate the expression of CLDN1 in non-small cell lung cancer (NSCLC) and its mechanism of action in cisplatin resistance.Material/MethodsA total of 55 patients with NSCLC admitted to our hospital between October 2013 and October 2015 were included. NSCLC tissues and tumor-adjacent tissues (≥5 cm from tumor edge) were collected. Among the 55 patients, 37 had adenocarcinoma and 18 had squamous cell carcinoma. Quantitative real-time polymerase chain reaction was used to determine mRNA expression, and protein expression was examined using Western blotting. CCK-8 assay was used to determine cell proliferation and Transwell assay was used to detect migration and invasion of the cells. Confocal microscopy was used to observe autophagosomes.ResultsIncreased CLDN1 expression promoted the development and metastasis of NSCLC. CLDN1 expression in A549/CDDP cells was up-regulated at both transcriptional and translational levels. Reduced CLDN1 expression decreased the drug resistance, proliferation, migration, and invasion abilities of A549/CDDP cells. Decreased CLDN1 expression promoted the apoptosis of A549/CDDP cells. CLDN1 enhanced CDDP drug resistance of A549 cells by activating autophagy. CLDN1 promoted the autophagy of A549 cells by up-regulating the phosphorylation level of ULK1.ConclusionsThe present study demonstrates that expression of CLDN1 in NSCLC is up-regulated and it is correlated with clinicopathological features. CLDN1 activates autophagy through up-regulation of ULK1 phosphorylation and promotes drug resistance of NSCLC cells to CDDP.

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Akt/mTOR mediated induction of bystander effect signaling in a nucleus independent manner in irradiated human lung adenocarcinoma epithelial cells

Cited by 11 publications

References 42 publications

Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs)

Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs)

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

CLDN1 Increases Drug Resistance of Non-Small Cell Lung Cancer by Activating Autophagy via Up-Regulation of ULK1 Phosphorylation

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