TFIIB-Related Factor 2 Is Associated with Poor Prognosis of Nonsmall Cell Lung Cancer Patients through Promoting Tumor Epithelial-Mesenchymal Transition

In this study, we found that increased BRF2 protein expression was prevalent in NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin, N-cadherin, and snail. Additionally, expression of BRF2 was found to be an independent prognostic factor in NSCLC patients. Furthermore, we showed that targeted knockdown of BRF2 expression could inhibit the migratory and invasive abilities of NSCLC cells and induced loss of the epithelial-mesenchymal transition of NSCLC cells. These results suggested that BRF2 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting epithelial-mesenchymal transition (EMT) program.

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Recent Advances in Elucidating Paclitaxel Resistance Mechanisms in Non-small Cell Lung Cancer and Strategies to Overcome Drug Resistance

Current Medicinal Chemistry ◽

10.2174/0929867326666191016113631 ◽

2020 ◽

Vol 27 (39) ◽

pp. 6573-6595

Author(s):

Hongmei Cui ◽

Kinsie Arnst ◽

Duane D. Miller ◽

Wei Li

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

Resistance Mechanisms ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Lung Cancer Patients ◽

Nsclc Patients

Paclitaxel (PTX) is a first-line drug for late-stage non-small cell lung cancer (NSCLC) patients who do not benefit from targeted therapy or immunotherapy. However, patients invariably develop resistance to PTX upon prolonged treatments. Although diverse mechanisms leading to PTX resistance have been well-documented in the literature, strategies to overcome PTX resistance in NSCLC based on these mechanisms are still challenging. In this article, we reviewed recent advancements elucidating major mechanisms of PTX resistance in NSCLC, including the overexpression of ABC transporters, alternations to tubulin structures, and the involvement of cytokines, miRNAs, kinase signaling pathways, and epithelial-mesenchymal transition. Potential markers of PTX resistance or PTX response that could help to direct treatment decisions and restore cellular sensitivity to PTX were also discussed. Finally, we summarized the corresponding strategies to overcome PTX resistance in NSCLC cells, which might provide new insights into clinical trials and benefit lung cancer patients in the future.

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Epithelial-mesenchymal transition-associated secretory phenotype predicts survival in lung cancer patients

Carcinogenesis ◽

10.1093/carcin/bgu041 ◽

2014 ◽

Vol 35 (6) ◽

pp. 1292-1300 ◽

Cited By ~ 24

Author(s):

A. K. Reka ◽

G. Chen ◽

R. C. Jones ◽

R. Amunugama ◽

S. Kim ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Lung Cancer Patients ◽

Secretory Phenotype

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Ursolic acid inhibits epithelial–mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells

Anti-Cancer Drugs ◽

10.1097/cad.0b013e328360093b ◽

2013 ◽

Vol 24 (5) ◽

pp. 494-503 ◽

Cited By ~ 23

Author(s):

Kunmei Liu ◽

Le Guo ◽

Lin Miao ◽

Weiwei Bao ◽

Jue Yang ◽

...

Keyword(s):

Lung Cancer ◽

Ursolic Acid ◽

Cell Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Nonsmall Cell Lung Cancer ◽

Mesenchymal Transition

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Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000488166 ◽

2018 ◽

Vol 45 (6) ◽

pp. 2213-2224 ◽

Cited By ~ 19

Author(s):

Meng Zhao ◽

Yahui Liu ◽

Ran Liu ◽

Jin Qi ◽

Yongwang Hou ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

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Abstract 3305: Markers of epithelial-mesenchymal transition as indicators of prognosis in lymph node aspirates from lung cancer patients

10.1158/1538-7445.am10-3305 ◽

2010 ◽

Author(s):

Patricia M. Watson ◽

Nicole T. Tanner ◽

Jessica S. Wang ◽

Nicholas J. Pastis ◽

Alice M. Boylan ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Cancer Patients ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Lung Cancer Patients

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Association of epithelial mesenchymal transition (EMT) markers and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.7550 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 7550-7550 ◽

Cited By ~ 1

Author(s):

N. B. Shah ◽

M. J. Fidler ◽

K. K. Walters ◽

E. Braun ◽

S. Basu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Outcome Measures ◽

Cell Lung Cancer ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Nsclc Patients ◽

Emt Markers

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BMI1,ALDH1A1, andCD133Transcripts Connect Epithelial-Mesenchymal Transition to Cancer Stem Cells in Lung Carcinoma

Stem Cells International ◽

10.1155/2016/9714315 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 20

Author(s):

Ana Koren ◽

Matija Rijavec ◽

Izidor Kern ◽

Eva Sodja ◽

Peter Korosec ◽

...

Keyword(s):

Lung Cancer ◽

Mrna Expression ◽

Whole Blood ◽

Epithelial Mesenchymal Transition ◽

Immunohistochemical Analysis ◽

Underlying Mechanism ◽

Primary Tumors ◽

Mesenchymal Transition ◽

Cellular Models ◽

Nsclc Patients

Epithelial-mesenchymal transition (EMT) is the underlying mechanism of tumor invasion and metastasis. Evidences from lung cancer cellular models show EMT can trigger conversion to a cancer stem cell (CSC) phenotype. In this study, we assessed mRNA expression levels of EMT-inducing transcription factors (BMI1,TWIST1), CSC (CD133,ALDH1A1), and epithelial (EpCAM) markers in primary tumor and whole blood samples obtained from 57 patients with operable non-small-cell lung cancer (NSCLC) as well as in circulating tumor cells (CTCs) of 13 patients with metastatic disease; then possible associations between marker expressions were evaluated. In primary tumors as well as in whole blood, correlations betweenBMI1andALDH1A1and betweenBMI1andCD133mRNA expressions were identified. No correlations betweenTWIST1and CSC markers were observed.BMI1mRNA expression in tumors positively correlated withBMI1mRNA expression in blood. The immunohistochemical analysis confirmed coexpression of BMI1 and CSC markers in tumors. Gene expression profiling in CTCs revealed upregulated expression of EMT/CSC markers in CTCs. Our results suggest CSCs are present in both, tumor tissue and blood of NSCLC patients, whereas Bmi1 may play an important role in initiation and maintenance of CSCs and might be involved in the blood-borne dissemination of NSCLC.

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TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.645402 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chunfeng Xie ◽

Jianyun Zhu ◽

Xue Yang ◽

Cong Huang ◽

Liping Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Tobacco Smoke ◽

Epithelial Mesenchymal Transition ◽

Suppressor Gene ◽

Inhibitory Effect ◽

Vimentin Expression ◽

Altered Expression ◽

Mesenchymal Transition ◽

Lung Cancer Patients ◽

Anti Cancer

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.

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Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p

The International Journal of Biological Markers ◽

10.1177/1724600817747524 ◽

2018 ◽

Vol 33 (2) ◽

pp. 148-155 ◽

Cited By ~ 23

Author(s):

Qiang Meng ◽

Bao-Ying Yang ◽

Bei Liu ◽

Ji-Xue Yang ◽

Yang Sun

Keyword(s):

Cell Proliferation ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Primary Brain Tumor ◽

Normal Brain ◽

Mesenchymal Transition ◽

Non Coding Rna ◽

Tumor Tissues ◽

Glioma Cell Proliferation ◽

Long Non Coding Rna

Introduction: Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. Methods: In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. Results: We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Conclusions: Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

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