Oxygenated Polycyclic aromatic hydrocarbons (Oxy-PAHs) facilitate lung cancer metastasis by epigenetically regulating the epithelial-to-mesenchymal transition (EMT)

2019 ◽  
Vol 255 ◽  
pp. 113261
Author(s):  
Dan Li ◽  
Yang Yun ◽  
Rui Gao
Keyword(s):  
Lung Cancer ◽  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Oxygenated Polycyclic Aromatic Hydrocarbons ◽  
Polycyclic Aromatic

scholarly journals MicroRNA in Lung Cancer Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 265 ◽  
Author(s):  
Shang-Gin Wu ◽  
Tzu-Hua Chang ◽  
Yi-Nan Liu ◽  
Jin-Yuan Shih
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Treatments ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Targeted Treatments

Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.

scholarly journals Vimentin is Required for Tumor Progression and Metastasis in a Mouse Model of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Alexandra L. Berr ◽  
Kristin Wiese ◽  
Gimena dos Santos ◽  
Jennifer M. Davis ◽  
Clarissa M. Koch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Differential Expression Analysis ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

AbstractVimentin, a type III intermediate filament, is highly expressed in aggressive epithelial cancers and is associated with increased rates of metastasis. We show that vimentin is causally required for lung cancer metastasis using a genetic mouse model of lung adenocarcinoma (LSL-KrasG12D;Tp53fl/fl, termed KPV+/+) crossed with vimentin-null mice (thereby creating KPV−/− mice). Both KPV+/+ and KPV−/− mice developed lung tumors, yet KPV−/− mice had delayed tumorigenesis and prolonged survival. KPV+/+ cells implanted in the flank metastasized to the lung while KPV−/− cells did not, providing additional evidence that vimentin is required for metastasis. Differential expression analysis of RNA-seq data demonstrated that KPV−/− cells had suppressed expression of genes that drive epithelial-to-mesenchymal transition, migration, and invasion, processes that are critical to the metastatic cascade. Integrative metabolomic and transcriptomic analysis revealed altered glutaminolysis, with KPV−/− cells accumulating glutathione, leading to impaired cell motility in response to oxidative stress. Together, these results show that loss of vimentin impairs epithelial-to-mesenchymal transition and regulation of the oxidative stress response, resulting in decreased metastasis in murine lung adenocarcinoma.

scholarly journals Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Thitita Unahabhokha ◽  
Pithi Chanvorachote ◽  
Boonchoo Sritularak ◽  
Jutarat Kitsongsermthon ◽  
Varisa Pongrakhananon
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT). Gigantol, a bibenzyl compound extracted from the Thai orchid,Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT), thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis.

scholarly journals Adenylate kinase-4 modulates oxidative stress and stabilizes HIF-1α to drive lung cancer metastasis

2017 ◽  
Author(s):  
Yi-Hua Jan ◽  
Tsung-Ching Lai ◽  
Chih-Jen Yang ◽  
Yuan-Feng Lin ◽  
Ming-Shyan Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adenylate Kinase ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Aerobic Glycolysis ◽  
Xenograft Model ◽  
Gene Signature ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

AbstractDisrupting signaling axes that are essential for tumor metastasis may provide therapeutic opportunity to cure cancer. We previously identified adenylate kinase 4 (AK4) as a biomarker of metastasis in lung cancer. Here we analyze AK4-associated metabolic gene signature and reveal HIF-1α is transcriptionally activated and associated with poor prognosis in lung adenocarcinoma patients. Overexpression of AK4 shifts metabolism towards aerobic glycolysis and elevates intracellular reactive oxygen species (ROS), which stabilizes and exaggerates HIF1-α protein expression and concurrently drives epithelial-to-mesenchymal transition (EMT) in hypoxia. Furthermore, overexpression of AK4 reduces hypoxic necrosis in tumors and promotes liver metastasis in vivo. Connectivity map analysis of AK4 gene signature identifies Withaferin-A as a potential compound to inhibit AK4-HIF-1α signaling axis, which then shows promising anti-metastatic potency in an orthotopic xenograft model of lung cancer. Our findings offer an alternative strategy to impair lung cancer metastasis via targeting AK4-HIF-1α axis.

scholarly journals The role of exosomes in lung cancer metastasis and clinical applications: an updated review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei Yin ◽  
Xiaotian Liu ◽  
Xuejun Shao ◽  
Tao Feng ◽  
Jun Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Value Assessment ◽  
Lung Carcinogenesis ◽  
Research Attention ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

AbstractLung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

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