scholarly journals PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1772
Author(s):  
Taek-In Oh ◽  
Mingyu Lee ◽  
Yoon-Mi Lee ◽  
Geon-Hee Kim ◽  
Daekee Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Lung Cancer ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Metastatic Lung

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial–mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

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.

A Case and Review of Bowel Perforation Secondary to Metastatic Lung Cancer

2005 ◽  
Vol 71 (2) ◽  
pp. 110-116 ◽  
Author(s):  
Robert A. Garwood ◽  
Mark D. Sawyer ◽  
E.J. Ledesma ◽  
Eugene Foley ◽  
Jeffrey A. Claridge
Keyword(s):  
Lung Cancer ◽  
Small Bowel ◽  
Cell Carcinoma ◽  
Cancer Metastasis ◽  
Bowel Perforation ◽  
Large Cell Carcinoma ◽  
Metastatic Lung Cancer ◽  
Small Bowel Perforation ◽  
Lung Cancer Metastasis ◽  
Metastatic Lung

Gastrointestinal tract perforation (GITP) secondary to metastatic lung cancer is extremely rare. We present a case of small bowel perforation secondary to metastatic lung cancer. The objective of this study was to review the current literature and further characterize the incidence, histology, and risk of GITP secondary to lung cancer metastasis. A Medline search was done to identify all the cases of GITP attributed to metastatic lung cancer reported in the literature. Data was collected and analyzed from a collection of cases in the medical literature since 1960. We identified 98 cases of perforated lung cancer metastasis to the small intestine. Four gastric perforations, three colonic perforations, and one appendiceal perforation were also identified but not analyzed. The mean age was 64.5 years. There was a male predominance of 89 per cent versus 11 per cent female. Perforations occurred most often in the jejunum (53%) followed by ileum (28%). Combined jejunum-ileum lesions accounted for 4 per cent of perforations. No duodenal perforations were reported, though a specific site was not determined in 13 per cent of cases. Small bowel perforations were most often caused by adenocarcinoma (23.7%), squamous cell carcinoma (22.7%), large cell carcinoma (20.6%), and small cell carcinoma (19.6%). The prevalence of small bowel perforation secondary to a given primary lung cancer histology varied by region. The mean survival was 66 days with 50 per cent of patients not surviving past 30 days. Despite a high incidence of lung cancer, small bowel perforation secondary to lung cancer metastasis remains relatively rare. Perforated metastases occur more often in men and are found more commonly in the jejunum. Small bowel perforations are caused most often by adenocarcinoma; however, squamous cell and large cell carcinoma metastases are more likely to result in perforation. Small bowel perforation in this setting has a significant impact on mortality, decreasing 1-year survival to less than 3 per cent.

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.

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells

2019 ◽  
Vol 400 (6) ◽  
pp. 765-776 ◽  
Author(s):  
Cun-en Wu ◽  
Yu-wen Zhuang ◽  
Jin-yong Zhou ◽  
Shen-lin Liu ◽  
Xi Zou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Allelic Deletion

Abstract The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1. Mechanistically, the Wnt/β-catenin signaling pathway was found to participate in the nm23-H1-mediated process. Besides, XAV939 prohibited cell EMT and stemness which could be impaired by knocking down of nm23-H1, while stable transfection of nm23-H1 attenuated hypoxia phonotype induced by lithium chloride (LiCl). Generally, our experiment provided evidence that nm23-H1 can reverse hypoxia induced EMT and stemness through the inhibition of the Wnt/β-catenin pathway, which may furnish a deeper perspective into the better treatment or prognosis for NSCLC.

scholarly journals Daxx inhibits hypoxia-induced lung cancer cell metastasis by suppressing the HIF-1α/HDAC1/Slug axis

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ching-Wen Lin ◽  
Lu-Kai Wang ◽  
Shu-Ping Wang ◽  
Yih-Leong Chang ◽  
Yi-Ying Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Cancer Invasion ◽  
Death Domain ◽  
Mesenchymal Transition ◽  
Histone Deacetylase 1 ◽  
Lung Cancer Metastasis

Abstract Hypoxia is a major driving force of cancer invasion and metastasis. Here we show that death domain-associated protein (Daxx) acts to negatively regulate hypoxia-induced cell dissemination and invasion by inhibiting the HIF-1α/HDAC1/Slug pathway. Daxx directly binds to the DNA-binding domain of Slug, impeding histone deacetylase 1 (HDAC1) recruitment and antagonizing Slug E-box binding. This, in turn, stimulates E-cadherin and occludin expression and suppresses Slug-mediated epithelial–mesenchymal transition (EMT) and cell invasiveness. Under hypoxic conditions, stabilized hypoxia-inducible factor (HIF)-1α downregulates Daxx expression and promotes cancer invasion, whereas re-expression of Daxx represses hypoxia-induced cancer invasion. Daxx also suppresses Slug-mediated lung cancer metastasis in an orthotopic lung metastasis mouse model. Using clinical tumour samples, we confirmed that the HIF-1α/Daxx/Slug pathway is an outcome predictor. Our results support that Daxx can act as a repressor in controlling HIF-1α/HDAC1/Slug-mediated cancer cell invasion and is a potential therapeutic target for inhibition of cancer metastasis.

scholarly journals Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel

2021 ◽  
Author(s):  
Samriddhi Arora ◽  
Jyoti Tanwar ◽  
Nutan Sharma ◽  
Suman Saurav ◽  
Rajender K. Motiani
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first time reports that Orai3 drives aggressive phenotypes of PC cells i.e. migration in vitro and metastasis in vivo. Considering that Orai3 expression is inversely associated with the PC patients survival time, it appears to be a highly attractive therapeutic target.

scholarly journals MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1193 ◽  
Author(s):  
Xing-Ning Lai ◽  
Jun Li ◽  
Li-Bo Tang ◽  
Wen-Tong Chen ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
High Morbidity ◽  
Dual Roles ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Non Coding Rnas

Lung cancer is one of the most malignant cancers around the world, with high morbidity and mortality. Metastasis is the leading cause of lung cancer deaths and treatment failure. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), two groups of small non-coding RNAs (nc-RNAs), are confirmed to be lung cancer oncogenes or suppressors. Transforming growth factor-β (TGF-β) critically regulates lung cancer metastasis. In this review, we summarize the dual roles of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer epithelial-mesenchymal transition (EMT), invasion, migration, stemness, and metastasis. In addition, lncRNAs, competing endogenous RNAs (ceRNAs), and circular RNAs (circRNAs) can act as miRNA sponges to suppress miRNAs, thereby mediating TGF-β signaling-regulated lung cancer invasion, migration, and metastasis. Through this review, we hope to cast light on the regulatory mechanisms of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer metastasis and provide new insights for lung cancer treatment.

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