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 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 Histone chaperone APLF level dictate implantation of mouse embryo

2020 ◽  
pp. jcs.246900
Author(s):  
Pallavi Chinnu Varghese ◽  
Sruthy Manuraj Rajam ◽  
Debparna Nandy ◽  
Aurelie Jory ◽  
Ananda Mukherjee ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Histone Chaperone ◽  
Breast Cancer Metastasis ◽  
Mouse Development ◽  
Mesenchymal Transition ◽  
Murine Fibroblast ◽  
Post Implantation

Our recent findings demonstrated that histone chaperone and DNA repair factor Aprataxin PNK like factor (APLF) could regulate Epithelial to mesenchymal transition (EMT) during reprogramming of murine fibroblast and in breast cancer metastasis. So, we investigated the function of APLF in EMT associated with mouse development. Here we show that APLF is predominantly enhanced in trophectoderm and lineages derived from trophectoderm in pre and post-implantation embryos. Downregulation of APLF induced hatching of embryos in vitro with a significant increase in Cdh1 and Cdx2 expression. Aplf shRNA microinjected embryos failed to implant in vivo. Rescue experiments neutralized the knockdown effects of APLF both in vitro and in vivo. Reduced expression of Snai2, Tead4 and the gain in Cdh1 and sFlt1 level marked the differentiation of APLF-knocked down Trophoblast Stem Cells that might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role of APLF during implantation and post-implantation development of mouse embryos. We anticipate that APLF might contribute to the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.

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.

Melatonin suppresses lung cancer metastasis by inhibition of epithelial–mesenchymal transition through targeting to Twist

2019 ◽  
Vol 133 (5) ◽  
pp. 709-722 ◽  
Author(s):  
Chia-Chia Chao ◽  
Po-Chun Chen ◽  
Pei-Chen Chiou ◽  
Chin-Jung Hsu ◽  
Po-I Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Stage ◽  
Bhlh Transcription Factor ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Twist Expression ◽  
Carcinogenic Substances

AbstractThe epithelial–mesenchymal transition (EMT) phenotype, whereby mature epithelial cells undergo phenotype transition and differentiate into motile, invasive cells, has been indicated in tumor metastasis. The melatonin hormone secreted by the pineal gland has an antioxidant effect and protects cells against carcinogenic substances that reduce tumor progression. However, the effects of melatonin in EMT and lung cancer metastasis are largely unknown. We found that melatonin down-regulated EMT by inhibiting Twist/Twist1 (twist family bHLH transcription factor 1) expression. This effect was mediated by MT1 receptor, PLC, p38/ERK and β-catenin signaling cascades. Twist expression was positively correlated with tumor stage and negatively correlated with MT1 expression in lung cancer specimens. Furthermore, melatonin inhibited EMT marker expression and lung cancer metastasis to liver in vivo. Finally, melatonin shows promise in the treatment of lung cancer metastasis and deserves further study.

scholarly journals Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells

2017 ◽  
Vol 313 (5) ◽  
pp. C556-C566 ◽  
Author(s):  
Phattrakorn Powan ◽  
Sudjit Luanpitpong ◽  
Xiaoqing He ◽  
Yon Rojanasakul ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Formation ◽  
Lung Cancer Cells ◽  
Tumor Spheroid ◽  
Mesenchymal Transition ◽  
E Cadherin

The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers.

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