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Epithelial to mesenchymal transition lung

Siyang Feng, Jianxue Zhai, Di Lu, Jie Lin, Xiaoying Dong, Xiguang Liu, Hua Wu, Anja C Roden, Giovanni Brandi, Simona Tavolari, Andrea Bille, Kaican Cai
Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines...
August 8, 2018: Experimental Cell Research
Hiroki Sato, Hiromasa Yamamoto, Masakiyo Sakaguchi, Kazuhiko Shien, Shuta Tomida, Tadahiko Shien, Hirokuni Ikeda, Minami Hatono, Hidejiro Torigoe, Kei Namba, Takahiro Yoshioka, Eisuke Kurihara, Yusuke Ogoshi, Yuta Takahashi, Junichi Soh, Shinichi Toyooka
Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non-small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide-3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR-TKI-resistant NSCLC cell lines...
August 10, 2018: Cancer Science
Mingyue Li, Grace Gar-Lee Yue, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Clara Bik-San Lau
BACKGROUND: Curcumin, a well-studied component in turmeric, exhibits potent antitumor effects in colorectal cancer. Previous studies showed that turmerones raised the accumulation of curcumin inside colonic cells, and curcumin present in turmeric ethanolic extract had enhanced anti-tumor activities in mice. Metastasis accounts for more than 90% colorectal cancer deaths. However, the anti-metastatic effect of turmeric extract on colorectal cancer is still unknown. METHODS: In the present study, colony formation, scratch, transwell and Western blot were used to assess colony formation, motility, migration and underlying mechanisms in vitro, respectively...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Guodong Xiao, Yuan Li, Meng Wang, Xiang Li, Sida Qin, Xin Sun, Rui Liang, Boxiang Zhang, Ning Du, Chongwen Xu, Hong Ren, Dapeng Liu
OBJECTIVES: FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin-mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear. MATERIALS AND METHODS: Immunohistochemical staining and qRT-PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour-adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere-formation assays...
August 9, 2018: Cell Proliferation
Girish Talakatta, Mohsen Sarikhani, Jaseer Muhamed, K Dhanya, Bagganahalli S Somashekar, Padukudru Anand Mahesh, Nagalingam Sundaresan, P V Ravindra
In the long term, diabetes profoundly affects multiple organs, such as the kidney, heart, brain, liver, and eyes. The gradual loss of function in these vital organs contributes to mortality. Nonetheless, the effects of diabetes on the lung tissue are not well understood. Clinical and experimental data from our studies revealed that diabetes induces inflammatory and fibrotic changes in the lung. These changes were mediated by TGF-β-activated epithelial-to-mesenchymal transition (EMT) signaling pathways. Our studies also found that glucose restriction promoted mesenchymal-to-epithelial transition (MET) and substantially reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT was mediated in part by the effects of hyperglycemia...
August 9, 2018: Scientific Reports
Fang-Lin Zhang, Jin-Ling Cao, Hong-Yan Xie, Rui Sun, Li-Feng Yang, Zhi-Ming Shao, Da-Qiang Li
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with a high propensity for distant metastasis and limited treatment options, yet its molecular underpinnings remain largely unknown. Microrchidia family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein whose mutations have been causally implicated in several neurological disorders. Here we report that a cancer-associated substitution of methionine to isoleucine at residue 276 (M276I) of MORC2 confers gain-of-function properties in the metastatic progression of TNBC...
August 9, 2018: Cancer Research
Kuang-Tai Kuo, Wen-Chien Huang, Oluwaseun Adebayo Bamodu, Wei-Hwa Lee, Chun-Hua Wang, M Hsiao, Liang-Shun Wang, Chi-Tai Yeh
BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. METHODS: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines...
August 9, 2018: Clinical Epigenetics
Haizhu Zeng, Yumeng Wang, Yuxia Gu, Jinrui Wang, Huali Zhang, Hongchang Gao, Qinqin Jin, Lei Zhao
Reactive oxygen species (ROS) and epithelial-mesenchymal transition (EMT) play a critical role in transforming growth factor (TGF)-β1-mediated fibrotic airway remodeling in asthma. Polydatin (PD) is a small natural molecule in Chinese medicine; it is isolated from Polygonum cuspidatum and has antioxidative properties. In this study, we aimed to determine whether PD was protective against ROS-induced pulmonary fibrosis in asthma. Ovalbumin (OVA) was used to induce asthma in a mouse model that was treated with or without PD...
August 6, 2018: Life Sciences
Oshrat Attar-Schneider, Liat Drucker, Maya Gottfried
The fatality of non-small-cell lung cancer (NSCLC) and the role of the cancer microenvironment in its resistance to therapy are long recognized. Accumulating data allocate a significant role for mesenchymal stem cells (MSCs) in the malignant environment. Previously, we have demonstrated that MSCs from NSCLC metastatic bone marrow (BM) niche deleteriously affected NSCLC cells. Here, we have decided to examine the effect of MSCs from the primary niche of the lung (healthy or adjacent to tumor) on NSCLC phenotype...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Payal Mitra, Pazhanichamy Kalailingam, Hui Bing Tan, Thirumaran Thanabalu
GRB2 is an adaptor protein which interacts with phosphorylated TGF-β receptor and is critical for mammary tumour growth. We found that TGF-β1-induced EMT increased GRB2 expression in A549 cells (non-small cell lung cancer). Overexpression of GRB2 (A549GRB2 ) enhanced cell invasion while knocking down GRB2 (A549GRB2KD ) reduced cell migration and invasion, probably due to increased vinculin and reduced Paxillin patches in A549GRB2KD cell. TGF-β1-induced EMT was more pronounced in A549GRB2 cells and attenuated in A549GRB2KD cells...
August 7, 2018: Cells
Xia Li, Junzhou Wu, Xiaoying Zhang, Wei Chen
Malignant melanoma is a highly metastatic and life-threatening cancer. Reactive oxygen species (ROS) play important roles in cancer initiation and progression including metastasis. It has been reported that the oxidative stress spontaneously generated in circulating melanoma cells was able to suppress distant metastasis in vivo. However, little is known regarding the effects and mechanism of glutathione reductase (GR) inhibition-induced oxidative stress in regulation of melanoma metastasis. Here, we demonstrate that GR inhibition generates oxidative stress and suppresses lung metastasis and subcutaneous growth of melanoma in vivo...
August 4, 2018: Free Radical Biology & Medicine
Fu-Chun Huo, Yao-Jie Pan, Tong-Tong Li, Jie Mou, Dong-Sheng Pei
p21-activated kinase 5 (PAK5) is involved in several oncogenic signaling pathways and its amplification or overexpression has been found in various types of cancer; however, the pathophysiologic role of PAK5 in cervical cancer (CC) remains elusive. This study aims to elucidate the effects of PAK5 on CC metastasis and its specific regulation mechanism. We performed western blotting and immunohistochemistry (IHC) analysis and found that the expression levels of PAK5 were significantly upregulated in CC cells and tissues...
August 6, 2018: Cell Death and Differentiation
Hui Zhong, Abdelkader Daoud, Jichun Han, Xiaohong An, Caili Qiao, Lanlan Duan, Yichuan Wang, Zhenfeng Chen, Jia Zhou, Jing Shang
Targeting tumor microenvironment (TME) is crucial in order to overcome the anti-cancer therapy resistance. In this study, we report the antitumor activity of a newly synthesized β-carboline derivative "B-9-3." Here, this small molecule showed a promising antitumor activity in vivo along with an enhanced immune response as reflected by a reduction of regulatory T cells and increased CD4+/CD8+ T cells. Further, B-9-3 decreased the number of myofibroblasts not only in the tumor but also in the lung suggesting an anti-metastatic action...
2018: Frontiers in Pharmacology
Adela García-Martín, Martín Garrido-Rodríguez, Carmen Navarrete, Carmen Del Río, María L Bellido, Giovanni Appendino, Marco A Calzado, Eduardo Muñoz
Systemic sclerosis (SSc) or scleroderma is a chronic multi-organ autoimmune disease characterized by vascular, immunological, and fibrotic abnormalities. The etiology of SSc is unknown, but there is growing evidence that dysfunction of the endocannabinoid system (ECS) plays a critical role in its development. Since the semi-synthetic cannabinoquinoid VCE-004.8 could alleviate bleomycin (BLM)-induced skin fibrosis, we have investigated an oral lipid formulation (EHP-101) of this dual PPARγ/CB2 receptors activator for the prevention of skin- and lung fibrosis and of collagen accumulation in BLM challenged mice...
August 1, 2018: Biochemical Pharmacology
Imène Hamaidi, Catherine Coquard, Sabrina Danilin, Valérian Dormoy, Claire Béraud, Sylvie Rothhut, Mariette Barthelmebs, Nadia Benkirane-Jessel, Véronique Lindner, Hervé Lang, Thierry Massfelder
Metastatic clear cell renal cell carcinoma (CCC) remains incurable despite advances in the development of anti-angiogenic targeted therapies and the emergence of immune checkpoint inhibitors. We have previously shown that the sonic hedgehog-Gli signaling pathway is oncogenic in CCC allowing us to identify the developmental Lim1 transcription factor as a Gli target and as a new oncogene in CCC regulating cell proliferation and apoptosis, and promoting tumor growth. In this previous study, preliminary in vitro results also suggested that Lim1 may be implicated in metastatic spread...
August 3, 2018: Oncogene
Chun-Xiao Fang, Chun-Mei Ma, Ling Jiang, Xi-Ming Wang, Na Zhang, Ji-Na Ma, Tai-Hua Wu, Zhong-He Zhang, Guang-Dong Zhao, Ya-Dong Zhao
Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast foci in lung parenchyma. Myofibroblasts are thought to originate from epithelial-to-mesenchymal transition (EMT). Wnt1 and lithium chloride (LiCl) induce EMT in alveolar epithelial cells (AECs), but the mechanisms are unclear. AECs were treated with Wnt1 and LiCl, respectively; morphological change and molecular changes of EMT, including E-cadherin, fibronectin, and vimentin, were observed. SB203580 was administrated to test the role of p38 МАРК signaling in EMT...
June 2018: Current medical science
Qinqin Pu, Yuanyu Zhao, Yuyang Sun, Ting Huang, Ping Lin, Chuanmin Zhou, Shugang Qin, Brij B Singh, Min Wu
Airway remodeling with progressive epithelial alterations in the respiratory tract is a severe consequence of asthma. Although dysfunctional signaling transduction is attributed to airway inflammation, the exact mechanism of airway remodeling remains largely unknown. TRPC1, a member of the transient receptor potential canonical Ca2+ channel family, possesses versatile functions but its role in airway remodeling remains undefined. Here, we show that ablation of TRPC1 in mice alleviates airway remodeling following house dust mite (HDM) challenge with decreases in mucus production, cytokine secretion, and collagen deposition...
August 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Qiulin Tang, Mingxing Li, Liang Chen, Feng Bi, Hongwei Xia
Lung cancer is a major cause of mortality worldwide and non‑small cell lung cancer (NSCLC) accounts for ~80% of all cases of lung cancer. Increasing evidence indicates that Rho family GTPase 3 (RhoE) is important in the carcinogenesis and progression of NSCLC. In addition, several studies have indicated that microRNA (miR)‑200b/c is downregulated in NSCLC cells. However, the exact mechanism remains to be elucidated. In the present study, immunohistochemistry (IHC) assays were used to analyze the RhoE and epithelial‑mesenchymal transition (EMT)‑related proteins in NSCLC tissues...
July 20, 2018: International Journal of Oncology
Qi Yin, Yang Han, Dongyi Zhu, Zhanxia Li, Shan Shan, Wenjing Jin, Qingchun Lu, Tao Ren
Background: MicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). Here, we investigated the role of miR-145 and miR-497 in TGF-β-induced epithelial-mesenchymal transition (EMT) process of NSCLC. Methods: We performed quantitative real time PCR (qRT-PCR) to detect the expression level of miR-145 and miR-497 in NSCLC cell lines. Then in the presence/absence of TGF-β, we transfected miRNA mimics or inhibitor into A549 and H1299 cells and investigated the role of miR-145 and miR-497 in cell migration and invasion using transwell and wound-healing assay...
2018: Cancer Cell International
Jeehan Lee, Hye Hyeon Yun, Seulki Kim, Sang Hee Ji, Hyo-Jeong Kuh, Jeong-Hwa Lee
BACKGROUND/AIM: High expression of the Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic protein, in various human cancers is linked to a poor outcome. The purpose of this study was to clarify whether BIS is associated with the migration and invasive characteristics of A549 cells. MATERIALS AND METHODS: BIS-knockout (KO) cells were prepared by the CRISPR/Cas9 method. The aggressive behaviors of A549 cells were analyzed by wound healing and a transwell invasion assay as well as 3D spheroid culture...
August 2018: Anticancer Research
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