scholarly journals CUB Domain-Containing Protein 1 Is a Novel Regulator of Anoikis Resistance in Lung Adenocarcinoma

2007 ◽  
Vol 27 (21) ◽  
pp. 7649-7660 ◽  
Author(s):  
Takamasa Uekita ◽  
Lin Jia ◽  
Mako Narisawa-Saito ◽  
Jun Yokota ◽  
Tohru Kiyono ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
A549 Cells ◽  
Metastatic Potential ◽  
Lung Cancer Cells ◽  
Anoikis Resistance ◽  
Cub Domain ◽  
Specific Disorders

ABSTRACT Malignant tumor cells frequently achieve resistance to anoikis, a form of apoptosis induced by detachment from the basement membrane, which results in the anchorage-independent growth of these cells. Although the involvement of Src family kinases (SFKs) in this alteration has been reported, little is known about the signaling pathways involved in the regulation of anoikis under the control of SFKs. In this study, we identified a membrane protein, CUB-domain-containing protein 1 (CDCP1), as an SFK-binding phosphoprotein associated with the anchorage independence of human lung adenocarcinoma. Using RNA interference suppression and overexpression of CDCP1 mutants in lung cancer cells, we found that tyrosine-phosphorylated CDCP1 is required to overcome anoikis in lung cancer cells. An apoptosis-related molecule, protein kinase Cδ, was found to be phosphorylated by the CDCP1-SFK complex and was essential for anoikis resistance downstream of CDCP1. Loss of CDCP1 also inhibited the metastatic potential of the A549 cells in vivo. Our findings indicate that CDCP1 is a novel target for treating cancer-specific disorders, such as metastasis, by regulating anoikis in lung adenocarcinoma.

scholarly journals 3,5-Dimethyaminophenol is not Mutagenic in Ames Test and HPRT Test and may have Anti-Carcinogenic Potential Against Lung Cancer Cells

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1553
Author(s):  
Ming-Wei Chao ◽  
Chia-Yi Tseng ◽  
Pei-Ying Lin ◽  
Yu-Jung Chang ◽  
Özge Köse ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Salmonella Typhimurium ◽  
Cancer Cells ◽  
Cho Cells ◽  
Ames Test ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Lung Fibroblasts ◽  
Carcinogenic Potential

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. However, we have shown that this alkylaniline metabolite was non-mutagenic to different strains of Salmonella typhimurium in Ames test and also was found to be not mutagenic to CHO cells in HPRT test. Concerning all the available data, we aimed to observe whether this metabolite may have anti-carcinogenic potential in human non-small cell lung cancer line (A549 cells). 3,5-DMAP caused a dose-dependent increase in cytotoxicity and generation of superoxide (O2-.) and reactive oxygen species (ROS). 3,5-DMAP did not produce significant cytotoxicity to human lung fibroblasts even at very high concentrations; however showed higher cytotoxic effect on A549 lung cancer cells at the same concentrations. 3,5-DMAP also led to molecular events, like increases in apoptotic markers (i.e., p53, Bad, Bax and cytochrome and decreases anti-apoptotic proteins (Bcl-2). Furthermore, 3,5-DMAP provided significant decreases in cell viability of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. In conclusion, our findings demonstrate 3,5-DMAP is not mutagenic to Salmonella typhimurium and CHO cells; toxic to A549 cells and therefore may have anti-cancer properties, the importance of which should be elucidated with further mechanistic studies.

scholarly journals Knockdown of RAD54B expression reduces cell proliferation and induces apoptosis in lung cancer cells

2019 ◽  
Vol 47 (11) ◽  
pp. 5650-5659 ◽  
Author(s):  
Chuan Xu ◽  
Di Liu ◽  
Hong Mei ◽  
Jian Hu ◽  
Meng Luo
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Caspase 3 ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Gene And Protein Expression ◽  
Healthy Lung

Objective RAD54 homolog B (RAD54B), a member of the SNF2/SWI2 superfamily, is implicated in homologous recombination, and high RAD54B expression predicts the prognostic outcomes of lung adenocarcinoma. However, its role in lung carcinogenesis was unclear so this was determined in the present study. Methods We evaluated the gene and protein expression of RAD54B in 15 lung adenocarcinoma tissues and matched adjacent healthy lung tissues by real-time PCR, immunohistochemical staining, and western blotting. A549 lung cancer cells were transduced with lentivirus carrying small hairpin RNA (shRNA) against RAD54B (shRAD54B) or control shRNA (shCtrl), and cell proliferation, viability, apoptosis, and caspase 3/7 activity were evaluated. Results RAD54B protein expression was significantly higher in lung adenocarcinoma tissues than in healthy lung tissues. RAD54B gene expression was high in A549 cells but was efficiently knocked down using shRAD54B with an infection efficiency of 80% and a knockdown ratio of 72.2% compared with shCtrl. Suppressing RAD54B expression in A549 cells significantly reduced cell proliferation and caspase 3/7 activity, and significantly increased the apoptotic rate. Conclusions RAD54B exerts an oncogenic role in lung cancer cell proliferation.

BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells

2004 ◽  
Vol 286 (1) ◽  
pp. L81-L86 ◽  
Author(s):  
S. Buckley ◽  
W. Shi ◽  
B. Driscoll ◽  
A. Ferrario ◽  
K. Anderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Telomerase Activity ◽  
Lung Cancer Cells ◽  
Senescent Phenotype ◽  
A549 Lung

Lung cancer is the most common visceral malignancy in males, with rapidly increasing incidence in females, and a devastatingly poor prognosis. Transforming growth factor (TGF)-β has been shown to induce senescence in A549 lung cancer cells, and both TGF-β and bone morphogenetic protein (BMP) 2 can suppress the transformed phenotype of A549 cells in vitro. We examined the effects of BMP4, another member of the TGF-β superfamily, on specific oncogenic properties of A549 cancer cells. When A549 cancer cells were treated continuously with 100 ng/ml of BMP4, a senescent phenotype was observed after 2 wk of treatment. The BMP-treated cells appeared larger than untreated cells, grew more slowly, had more senescence-associated β-galactosidase activity, and had less telomerase activity, as measured by the telomeric repeat amplification protocol assay. Invasion through Engelbreth Holm-Swarm matrix was inhibited in the senescent cell population. Senescent BMP4-treated cells had lower ERK activation, VEGF expression, and Bcl2 expression than wild-type cells, consistent with a less proliferative, less angiogenic phenotype with increased susceptibility to death by apoptosis. BMP4 treatment also resulted in sustained elevation of Smad1. In vivo xenograft studies in the flanks of nude mice confirmed that the BMP-treated cells were significantly less tumorigenic than untreated cells. Direct overexpression of Smad1 using adenoviral constructs resulted in cell death within 5 days. These studies suggest that BMP4 pathway signaling can induce senescence and thus negatively regulate the growth of A549 lung cancer cells.

scholarly journals The intrinsic role and mechanism of tumor expressed-CD38 on lung adenocarcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Long Gao ◽  
Yuan Liu ◽  
Xiaohong Du ◽  
Sai Ma ◽  
Minmin Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Enzymatic Activity ◽  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
In Vitro Assays ◽  
Knock Out

AbstractIt has been recently reported that CD38 expressed on tumor cells of multiple murine and human origins could be upregulated in response to PD-L1 antibody therapy, which led to dysfunction of tumor-infiltrating CD8+ T immune cells due to increasing the production of adenosine. However, the role of tumor expressed-CD38 on neoplastic formation and progression remains elusive. In the present study, we aimed to delineate the molecular and biochemical function of the tumor-associated CD38 in lung adenocarcinoma progression. Our clinical data showed that the upregulation of tumor-originated CD38 was correlated with poor survival of lung cancer patients. Using multiple in vitro assays we found that the enzymatic activity of tumor expressed-CD38 facilitated lung cancer cell migration, proliferation, colony formation, and tumor development. Consistently, our in vivo results showed that inhibition of the enzymatic activity or antagonizing the enzymatic product of CD38 resulted in the similar inhibition of tumor proliferation and metastasis as CD38 gene knock-out or mutation. At biochemical level, we further identified that cADPR, the mainly hydrolytic product of CD38, was responsible for inducing the opening of TRPM2 iron channel leading to the influx of intracellular Ca2+ and then led to increasing levels of NRF2 while decreasing expression of KEAP1 in lung cancer cells. These findings suggested that malignant lung cancer cells were capable of using cADPR catalyzed by CD38 to facilitate tumor progression, and blocking the enzymatic activity of CD38 could be represented as an important strategy for preventing tumor progression.

scholarly journals UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinhong Zhu ◽  
Haijiao Ao ◽  
Mingdong Liu ◽  
Kui Cao ◽  
Jianqun Ma
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Risk Score ◽  
A549 Cells ◽  
Mtor Signaling ◽  
Lung Cancer Cells ◽  
Mtor Signaling Pathway

Abstract Background Ubiquitin-conjugating enzyme E2T (UBE2T) acts as an oncogene in various types of cancer. However, the mechanisms behind its oncogenic role remain unclear in lung cancer. This study aims to explore the function and clinical relevance of UBE2T in lung cancer. Methods Lentiviral vectors were used to mediate UBE2T depletion or overexpress UBE2T in lung cancer cells. CCK8 analysis and western blotting were performed to investigate the effects of UBE2T on proliferation, autophagy, and relevant signaling pathways. To exploit the clinical significance of UBE2T, we performed immunohistochemistry staining with an anti-UBE2T antibody on 131 NSCLC samples. Moreover, we downloaded the human lung adenocarcinoma (LUAD) dataset from The Cancer Atlas Project (TCGA). Lasso Cox regression model was adopted to establish a prognostic model with UBE2T-correlated autophagy genes. Results We found that UBE2T stimulated proliferation and autophagy, and silencing this gene abolished autophagy in lung cancer cells. As suggested by Gene set enrichment analysis, we observed that UBE2T downregulated p53 levels in A549 cells and vice versa. Blockade of p53 counteracted the inhibitory effects of UBE2T depletion on autophagy. Meanwhile, the AMPK/mTOR signaling pathway was activated during UBE2T-mediated autophagy, suggesting that UBE2T promotes autophagy via the p53/AMPK/mTOR pathway. Interestingly, UBE2T overexpression increased cisplatin-trigged autophagy and led to cisplatin resistance of A549 cells, whereas inhibiting autophagy reversed drug resistance. However, no association was observed between UEB2T and overall survival in a population of 131 resectable NSCLC patients. Therefore, we developed and validated a multiple gene signature by considering UBE2T and its relevance in autophagy in lung cancer. The risk score derived from the prognostic signature significantly stratified LUAD patients into low- and high-risk groups with different overall survival. The risk score might independently predict prognosis. Interestingly, nomogram and decision curve analysis demonstrated that the signature’s prognostic accuracy culminated while combined with clinical features. Finally, the risk score showed great potential in predicting clinical chemosensitivity. Conclusions We found that UBE2T upregulates autophagy in NSCLC cells by activating the p53/AMPK/mTOR signaling pathway. The clinical predicting ability of UBE2T in LUAD can be improved by considering the autophagy-regulatory role of UBE2T.

Downregulation of CPA4 to suppress NSCLC proliferation by inducing apoptosis and G1 arrest.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20074-e20074
Author(s):  
Yangyang Fu ◽  
Xiaoying Huang ◽  
Liangxing Wang
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Normal Lung ◽  
G1 Arrest ◽  
Cancer Aggressiveness

e20074 Background: Carboxypepidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Previous study discovered that CPA4 may participate in cell growth and differentiation of prostate epithelial cells. Meanwhile, CPA4 is a printed gene and thought to be involved in prostate cancer aggressiveness. As is reported, CPA4 was increased in NSCLC tissues compared to normal lung tissues and high expression of CPA4 was correlated with poor prognosis of NSCLC patients. However, the role of CPA4 play in lung tumorigenesis is still unclear. Methods: We examined the mRNA and protein expression level of CPA4 via real-time PCR and immunohistochemistry in NSCLC tissues and adjacent tissues. Growth assays both in vitro and in vivo were performed to elucidate the role of CPA4 may play in lung cancer and Fluorescence Activated Cell Sorter was conducted to uncover the putative mechanism. Results: CPA4 expression was increased both in mRNA and protein levels in NSCLC tissues compared to adjacent tissues. MTT and colony formation assays showed that downregulation of CPA4 in H1299 and A549 cells inhibited lung cancer cells proliferation. We further confirmed this result by using cellomics and celligo. Depleting CPA4 also suppressed tumor growth in mice. Mechanically, we found that suppressing CPA4 expression in lung cancer cells could induce apoptosis and G1 arrest. We supposed that CPA4 expression may be associated with caspase family and it needs further studies. Conclusions: Collectively, we demonstrate that decreased CPA4 inhibits NSCLC proliferation via inducing apoptosis and G1 arrest.

scholarly journals Berbamine Inhibits Cell Proliferation and Migration and Induces Cell Death of Lung Cancer Cells via Regulating c-Maf, PI3K/Akt, and MDM2-P53 Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Lili Liu ◽  
Zhiying Xu ◽  
Binbin Yu ◽  
Li Tao ◽  
Ying Cao
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Colony Formation ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
And Migration ◽  
Proliferation And Migration

Berbamine (BBM) is a natural product isolated from Berberis amurensis Rupr. We investigated the influence of BBM on the cell viability, proliferation, and migration of lung cancer cells and explored the possible mechanisms. The cell viability and proliferation of lung cancer cells were evaluated by MTT assay, EdU assay, and colony formation assay. Migration and invasion abilities of cancer cells were determined through wound scratch assay and Transwell assay. Cell death was evaluated by cell death staining assay and ELISA. The expressions of proteins were evaluated using western blot assay. A xenograft mouse model derived from non-small-cell lung cancer cells was used to detect the effect of BBM on tumor growth and metastasis in vivo. Both colony formation and EdU assays results revealed that BBM (10 μM) significantly inhibited the proliferation of A549 cells ( P < 0.001 ). BBM (10 μM) also significantly inhibited the migration and invasion ability of cancer cells in wound scratch and Transwell assays. Trypan blue assay and ELISA revealed that BBM (20 μM) significantly induced cell death of A549 cells. In xenograft mouse models, the tumor volume was significantly smaller in mice treated with BBM (20 mg/kg). The western blotting assay showed that BBM inhibited the PI3K/Akt and MDM2-p53 signaling pathways, and BBM downregulated the expression of c-Maf. Our results show that BBM inhibits proliferation and metastasis and induces cell death of lung cancer cells in vitro and in vivo. These effects may be achieved by BBM reducing the expression of c-Maf and regulating the PI3K/Akt and MDM2-p53 pathways.

scholarly journals ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Qingyang Ma ◽  
Kai Wu ◽  
Hui Li ◽  
Huichun Li ◽  
Yufei Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Specific Gene ◽  
Polycomb Repressive Complex 2 ◽  
Ectopic Activation

AbstractAberrant differentiation, driven by activation of normally silent tissue-specific genes, results in a switch of cell identity and often leads to cancer progression. The underlying genetic and epigenetic events are largely unexplored. Here, we report ectopic activation of the hepatobiliary-, intestinal- and neural-specific gene one cut homeobox 2 (ONECUT2) in various subtypes of lung cancer. ONECUT2 expression was associated with poor prognosis of RAS-driven lung adenocarcinoma. ONECUT2 overexpression promoted the malignant growth and invasion of A549 lung cancer cells in vitro, as well as xenograft tumorigenesis and bone metastases of these cells in vivo. Integrative transcriptomics and epigenomics analyses suggested that ONECUT2 promoted the trans-differentiation of lung cancer cells by preferentially targeting and regulating the activity of bivalent chromatin domains through modulating Polycomb Repressive Complex 2 (PRC2) occupancy. Our findings demonstrate that ONECUT2 is a lineage-specific and context-dependent oncogene in lung adenocarcinoma and suggest that ONECUT2 is a potential therapeutic target for these tumors.

scholarly journals Sevoflurane induces lung cancer cell apoptosis via inhibition of the expression of miRNA155 gene

2021 ◽  
Vol 20 (1) ◽  
pp. 69-74
Author(s):  
Huaizhao Wang ◽  
Bin Wang ◽  
Jingyan Jing ◽  
Na Li
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Lung Cancer Cells ◽  
Control Group ◽  
Sevoflurane Group ◽  
Lung Adenocarcinoma A549

Purpose: To determine the apoptotic effect of sevoflurane on lung cancer cells, and the underlying mechanism of action.Methods: Lung adenocarcinoma A549 cells were cultured for 24 h and divided into control group, 1% sevoflurane group and 3% sevoflurane group. The two levels of sevoflurane were provided through a gas monitor connected to each of the sevoflurane groups. The control group was not treated. Flow cytometry was used to analyze A549 cell apoptosis, while qRT-PCR was used for assay of the levels of miRNA155 in A549 cells. The protein expression of Bcl-2 was determined with immunoblotting. The percentage of apoptosis and levels of miRNA155 and Bcl-2 in the two cell lines were compared.Results: Significant differences in miRNA146a level were seen between the 3 % sevoflurane and control groups at 3 h. There was higher apoptosis in the 3 % sevoflurane group, relative to control, but miRNA155 levels in the 3 % sevoflurane group were generally less than that of the control (p < 0.05). There was lower Bcl-2 content in the 3 % sevoflurane group than in control group (p < 0.05).Conclusion: Sevoflurane exerts strong apoptotic and anti-proliferative effects on lung adenocarcinoma A549 cells via a mechanism which may be related to the downregulation of miRNA155, thereby inhibiting the expression of anti-apoptotic protein Bcl-2. This provides a new direction for research on anti-lung adenocarcinoma drugs. Keywords: Sevoflurane, Lung cancer cells, Apoptosis, Inhibition, miRNA155, Expression, Induction

scholarly journals Silencing of LINC01279 is activated apoptosis and autophagy in lung cancer by regulating FAK/ERK via SIN3A

2021 ◽  
Author(s):  
Wenmei Su ◽  
Jiancong Wu ◽  
Xiaobi Huang ◽  
Xiaofang Li ◽  
Honglian Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Lung Cancer Cells ◽  
Loss Of Function

Abstract Background: In human lung adenocarcinoma (LUAD) tissues, Long noncoding RNA LINC01279 is significantly upregulated. However, the functions of LINC01279 in LUAD is yet to be clarified.Methods: In situ hybridization was employed to investigate the difference between expression of LINC01279 in LUAD and in normal tissues. The result of in situ hybridization is verified by qRT-PCR. Cytoplasmic and nuclear experiments showed that LINC01279 was mainly located in the cytoplasm of lung cancer cells. The loss of function experiment showed that LINC01279 could inhibit the proliferation, colony formation, invasion and migration of lung cancer cells. The interaction between SIN3A and LINC01279 was confirmed by RIP test. At the same time, through western bolt, we found that LINC01279 plays a key role in the regulation of apoptosis and autophagy in lung adenocarcinoma.Results: Our study confirmed that LINC01279 was upregulated in LUAD tissues, the knocking-down of which significantly inhibited the growth of LUAD cancer cells both in vitro and in vivo. Mechanistic investigations revealed that LINC01279 could directly interact with SIN3A and modulate the FAK and ERK protein expression in the cytoplasm. Moreover, the proteins of PARP and LC3B, P62, Beclin-1, respectively related with apoptosis and autophagy, were changed after LINC01279 siRNA. Conclusions: Taken together, our research found that LINC01279 which is significantly up-regulated in LUAD tissues and cell lines, and promotes the changes of FAK and ERK proteins in downstream pathways by combining with SIN3A, promotes the proliferation of LUAD cells, and inhibits apoptosis and autophagy. The results of this work illustrated how LINC01279 is part of a regulatory network that contributes to the oncogenesis of LUAD and proposed LINC01279 could be a potential target for LUAD diagnosis and treatment.

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