Molecular Mechanisms of Asbestos- and Silica-Induced Lung Cancer

2004 ◽  
Author(s):  
Fei Chen ◽  
Val Vallyathan
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms

scholarly journals Drug Tolerance to EGFR Tyrosine Kinase Inhibitors in Lung Cancers with EGFR Mutations

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1590
Author(s):  
Kenichi Suda ◽  
Tetsuya Mitsudomi
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Drug Tolerance ◽  
Lung Cancers ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Mutated

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) serve as the standard of care for the first-line treatment of patients with lung cancers with EGFR-activating mutations. However, the acquisition of resistance to EGFR TKIs is almost inevitable, with extremely rare exceptions, and drug-tolerant cells (DTCs) that demonstrate reversible drug insensitivity and that survive the early phase of TKI exposure are hypothesized to be an important source of cancer cells that eventually acquire irreversible resistance. Numerous studies on the molecular mechanisms of drug tolerance of EGFR-mutated lung cancers employ lung cancer cell lines as models. Here, we reviewed these studies to generally describe the features, potential origins, and candidate molecular mechanisms of DTCs. The rapid development of an optimal treatment for EGFR-mutated lung cancer will require a better understanding of the underlying molecular mechanisms of the drug insensitivity of DTCs.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals PRMT5 Promotes EMT Through Regulating Akt Activity in Human Lung Cancer

2021 ◽  
Vol 30 ◽  
pp. 096368972110017
Author(s):  
Jianhao Huang ◽  
Yonghua Zheng ◽  
Xiao Zheng ◽  
Bao Qian ◽  
Qi Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Akt Signaling ◽  
Lung Cancer Cells ◽  
Signaling Cascades ◽  
Human Lung Cancer ◽  
Mesenchymal Transition ◽  
Human Lung Cancer Cells

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo, using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

scholarly journals The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Norahayu Othman ◽  
Noor Hasima Nagoor
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
High Frequency ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Lung Carcinogenesis ◽  
The Past ◽  
Late Stage Diagnosis ◽  
Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

scholarly journals Possible involvement of the Hedgehog and PDPK1–Akt pathways in the growth and migration of small-cell lung cancer

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110165
Author(s):  
Naiwang Tang ◽  
Bin Hu ◽  
Yin Zhang ◽  
Zhiwei Chen ◽  
Ronghuan Yu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Patient Characteristics ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
And Migration ◽  
Proliferation And Migration

Background Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC. Methods The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells. Results PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression. Conclusions The interaction between the PDPK1–Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.

scholarly journals MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop

2018 ◽  
Vol 26 (3) ◽  
pp. 385-400 ◽  
Author(s):  
Dandan Li ◽  
Changjun He ◽  
Junfeng Wang ◽  
Yanbo Wang ◽  
Jianlong Bu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/p53 feedback loop.

scholarly journals NNK-Induced Lung Tumors: A Review of Animal Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hua-Chuan Zheng ◽  
Yasuo Takano
Keyword(s):  
Lung Cancer ◽  
Animal Model ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Genetic Mutation ◽  
Lung Tumors ◽  
Chemotherapeutic Agents ◽  
Signal Pathways ◽  
Lung Carcinogenesis

The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models.

scholarly journals Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives

2022 ◽  
Vol 12 ◽  
Author(s):  
Sicon Mitra ◽  
Uttpal Anand ◽  
Niraj Kumar Jha ◽  
Mahipal S. Shekhawat ◽  
Suchismita Chatterjee Saha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Black Pepper ◽  
Piper Nigrum ◽  
Molecular Formula ◽  
Cycle Arrest

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.

scholarly journals Association between cytokine gene polymorphisms and squamous cell lung cancer depending on the duration of smoking in men

2018 ◽  
Vol 16 (1) ◽  
pp. 60-69
Author(s):  
Lyudmila A. Gordeeva ◽  
Stella A. Mun ◽  
Elena N. Voronina ◽  
Elena G. Polenok ◽  
Alina D. Magatina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Polymorphism ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Squamous Cell Lung Cancer ◽  
Additional Risk Factor ◽  
Smoking Duration ◽  
Mechanisms Of Development ◽  
Length Analysis

Background. Squamous cell lung cancer (SCLC) is the most common form of lung cancer among men smokers. Mediators and products of inflammation can contribute to the initiation of carcinogenesis in smokers. The aim of study is to investigate the association between IL1B(rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), IL6 (rs1800795), IL10 (rs1800896) genes and SCLC depending on the duration of smoking in men. Materials and methods. We studied 324 patients with SCLC and 168 healthy men smokers. The typing of the IL1RN(rs2234663) gene polymorphism has analyzed by polymerase chain reaction (PCR). Detection of the IL1B (rs1143634) and IL6 (rs1800795) polymorphisms have performed by restriction fragment length analysis, as a restriction enzyme TaqI was used. The IL1B (rs16944), TNFA(rs1800629) and IL10 (rs1800896) genes polymorphisms have determined through TaqMan-real-time PCR. Results. The study showed, the age, duration of smoking and the number of cigarettes smoked per day were the main risk factors for SCLC in men (p < 0.0001). The IL6 -174G allele was detected an additional risk factor of SCLC at a smoking duration of less than 35 years (OR = 1.68; 95 % CI: 1.12-2.51; pcor = 0,04). No association of IL1B (rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), and IL10 (rs1800896) genes with the risk of SCLC in men was identified. Conclusion. The duration of smoking and rs1800795 IL6 gene polymorphism may influence on the susceptibility to SCLC in men. Our results can be useful in understanding the molecular mechanisms of development of SCLC.

scholarly journals Molecular Inverse Comorbidity between Alzheimer’s disease and Lung Cancer: new insights from Matrix Factorization

2019 ◽  
Author(s):  
Alessandro Greco ◽  
Jon Sanchez Valle ◽  
Vera Pancaldi ◽  
Anaïs Baudot ◽  
Emmanuel Barillot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Matrix Factorization ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Biological Data ◽  
Biological Data Analysis ◽  
Specific Factors ◽  
Molecular Bases

AbstractMatrix Factorization (MF) is an established paradigm for large-scale biological data analysis with tremendous potential in computational biology.We here challenge MF in depicting the molecular bases of epidemiologically described Disease-Disease (DD) relationships. As use case, we focus on the inverse comorbidity association between Alzheimer’s disease (AD) and lung cancer (LC), described as a lower than expected probability of developing LC in AD patients. To the day, the molecular mechanisms underlying DD relationships remain poorly explained and their better characterization might offer unprecedented clinical opportunities.To this goal, we extend our previously designed MF-based framework for the molecular characterization of DD relationships. Considering AD-LC inverse comorbidity as a case study, we highlight multiple molecular mechanisms, among which the previously identified immune system and mitochondrial metabolism. We then discriminate mechanisms specific to LC from those shared with other cancers through a pancancer analysis. Additionally, new candidate molecular players, such as Estrogen Receptor (ER), CDH1 and HDAC, are pinpointed as factors that might underlie the inverse relationship, opening the way to new investigations. Finally, some lung cancer subtype-specific factors are also detected, suggesting the existence of heterogeneity across patients also in the context of inverse comorbidity.

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