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TGF Beta pathway in lung cancer

Wei Chen, Kai Zhao, Chenkui Miao, Aiming Xu, Jianzhong Zhang, Jundong Zhu, Shifeng Su, Zengjun Wang
The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis...
2017: OncoTargets and Therapy
Haitao Feng, Jin-Jian Lu, Yitao Wang, Lixia Pei, Xiuping Chen
Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST...
February 1, 2017: Cell Adhesion & Migration
Jun Li, Jie Ao, Kai Li, Jie Zhang, Yanyan Li, Le Zhang, Yuyan Wei, Di Gong, Junping Gao, Weiwei Tan, Lugang Huang, Lunxu Liu, Ping Lin, Yuquan Wei
Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells...
October 20, 2016: Cell Death & Disease
Yi-Fei Qi, Long Wu, Zi-Qian Li, Meng-Ling Wu, Hai-Fang Wang, Ka-Ying Chan, Lin-Lin Lu, Shao-Hui Cai, Hong-Sheng Wang, Jun Du
Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation...
October 15, 2016: Archives of Biochemistry and Biophysics
Chun-Lin Chen, Deng-Chyang Wu, Min-Yun Liu, Ming-Wei Lin, Hung-Tu Huang, Yaw-Bin Huang, Li-Chai Chen, Yu-Yu Chen, Jih-Jung Chen, Pei-Hua Yang, Yu-Chen Kao, Pei-Yu Chen
PURPOSE: The transforming growth factor-beta (TGF-β) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3-one, we aim to determine the effects of cholest-4-en-3-one on TGF-β signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. METHODS: The inhibitory effects of cholest-4-en-3-one on TGF-β-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF-β receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation...
April 2017: Journal of Receptor and Signal Transduction Research
Ji-Hua Nie, Zhi-Hai Chen, Chun-Lin Shao, Wei-Wei Pei, Jie Zhang, Shu-Yu Zhang, Yang Jiao, Jian Tong
The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA...
2016: Journal of Toxicology and Environmental Health. Part A
Saki Yokokura, Nobuhiro Kanaji, Akira Tadokoro, Shigeyuki Yokokura, Norimitsu Kadowaki, Shuji Bandoh
PURPOSE OF THE STUDY: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-β as a mechanism of CDR. MATERIALS AND METHODS: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions...
May 2016: Experimental Lung Research
Chunyou Wang, Pian Liu, Heshui Wu, Pengfei Cui, Yongfeng Li, Yao Liu, Zhiqiang Liu, Shanmiao Gou
Pancreatic ductal adenocarcinoma (PDAC), which accounts for 96% of all pancreatic cancer cases, is characterized by rapid progression, invasion and metastasis. Transforming growth factor-beta (TGF-β) signaling is an essential pathway in metastatic progression and microRNAs (miRNA) play central roles in the regulation of various biological and pathologic processes including cancer metastasis. However, the molecular mechanisms involved in regulation of miRNAs and activation of TGF-β signaling in PDAC remain to be established...
March 22, 2016: Oncotarget
Mariacarmela Santarpia, María González-Cao, Santiago Viteri, Niki Karachaliou, Giuseppe Altavilla, Rafael Rosell
A deeper understanding of the key role of the immune system in regulating tumor growth and progression has led to the development of a number of immunotherapies, including cancer vaccines and immune checkpoint inhibitors. Immune checkpoint inhibitors target molecular pathways involved in immunosuppression, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, with the goal to enhance the host's own immune anticancer response...
December 2015: Translational Lung Cancer Research
Runlong Lin, Shuai Yi, Linlin Gong, Weishuai Liu, Peng Wang, Ningbo Liu, Lujun Zhao, Ping Wang
PURPOSE: It was reported that halofuginone has inhibitory effects on transforming growth factor-beta (TGF-β) signaling pathway. The study was aimed to: 1) evaluate the antitumor effects of halofuginone in combination with radiation therapy; and 2) preliminarily explore the possible mechanisms associated with these effects. MATERIALS AND METHODS: Lewis lung cancer (LLC) cell lines and xenograft model mice randomly received ionizing radiation, halofuginone, or combination treatment...
2015: OncoTargets and Therapy
Yutaka Fujiwara, Hiroshi Nokihara, Yasuhide Yamada, Noboru Yamamoto, Kuniko Sunami, Hirofumi Utsumi, Hiroya Asou, Osamu TakahashI, Ken Ogasawara, Ivelina Gueorguieva, Tomohide Tamura
PURPOSE: Inhibition of transforming growth factor-beta receptor I (TGF-beta RI)-mediated signaling pathways blocks tumor growth and metastases in nonclinical studies. Galunisertib (LY2157299), a small molecule inhibitor of TGF-beta RI serine/threonine kinase, had antitumor effects with acceptable safety/tolerability in a first-in-human dose (FHD) study conducted mainly in Caucasian patients with glioma. In this nonrandomized, open-label, dose-escalation study, we assessed safety/tolerability, pharmacokinetics (PK), and tumor response in Japanese patients...
December 2015: Cancer Chemotherapy and Pharmacology
Hyeonseok Ko, Hyelin Jeon, Dahae Lee, Hyo-Kyoung Choi, Ki Sung Kang, Kyung-Chul Choi
In the epithelial-mesenchymal transition (EMT), an important cellular process, epithelial cells become mesenchymal cells. This process is also critically involved in cancer metastasis. Sanguiin H6 is a compound derived from ellagitannin, which is found in berries. Sanguiin H6 shows various pharmacological properties, including anti-angiogenic activity. Because the possible role of sanguiin H6 in the EMT and the underlying molecular mechanisms are unclear, we investigated the effect of sanguiin H6 on the EMT...
December 1, 2015: Bioorganic & Medicinal Chemistry Letters
Hye-Jin Ki, Se Yun Kim, Sang Ho Lee, Ju-Young Moon, Kyung Hwan Jeong, Tae Won Lee, Chun Gyoo Ihm, Su Kang Kim, Joo-Ho Chung, Sun Woo Kang, Tae Hee Kim, Yeong-Hoon Kim, Yang Gyun Kim
BACKGROUND: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in immune disorders, cancer, asthma, lung fibrosis, and chronic kidney disease, and its signal pathways are considered crucial mediators of a variety of cellular processes. In addition, several recent studies have reported that TGF-β receptor (TGF-βR) gene polymorphism is associated with chronic kidney disease. However, the association between end-stage renal disease (ESRD) and the TGF-β gene polymorphism has not been sufficiently investigated...
June 2015: Kidney Research and Clinical Practice
K O'Leary, A Shia, F Cavicchioli, V Haley, A Comino, M Merlano, F Mauri, K Walter, M Lackner, M B Wischnewsky, T Crook, C Lo Nigro, P Schmid
BACKGROUND: The transforming growth factor-beta (TGF- β) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF-β accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. METHODS: Methylation microarray and RNA sequencing were carried out on lung cancer cell lines...
September 15, 2015: British Journal of Cancer
Stephan Herbertz, J Scott Sawyer, Anja J Stauber, Ivelina Gueorguieva, Kyla E Driscoll, Shawn T Estrem, Ann L Cleverly, Durisala Desaiah, Susan C Guba, Karim A Benhadji, Christopher A Slapak, Michael M Lahn
Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway...
2015: Drug Design, Development and Therapy
Cedric Carl, Anne Flindt, Julian Hartmann, Markus Dahlke, Dirk Rades, Jürgen Dunst, Hendrik Lehnert, Frank Gieseler, Hendrik Ungefroren
Radiotherapy, a major treatment modality against cancer, can lead to secondary malignancies but it is uncertain as to whether tumor cells that survive ionizing radiation (IR) treatment undergo epithelial-mesenchymal transition (EMT) and eventually become invasive or metastatic. Here, we have tested the hypothesis that the application of IR (10 MeV photon beams, 2-20 Gy) to lung and pancreatic carcinoma cells induces a migratory/invasive phenotype in these cells by hyperactivation of TGF-β and/or activin signaling...
January 2016: Cellular and Molecular Life Sciences: CMLS
M Johnson, S Brennecke, A-C Iversen, C East, G Olsen, J Kent, T Dyer, J Said, L Roten, L Abraham, J-A Zwart, B Winsvold, A Håberg, M Huentelman, H Krokan, M Gabrielsen, R Austgulen, J Blangero, E Moses
INTRODUCTION: We have successfully utilized a family-based study design to localize several positional candidate preeclampsia susceptibility genes to chromosomes 2q22(ACVR2A,LCT,LRP1B,RND3,GCA),5q (ERAP2) and 13q(TNFSF13B). We now report on our continued positional cloning efforts using an alternative genome-wide association (GWA) mapping strategy in large Caucasian case-control cohorts from Australia and Norway. OBJECTIVES: To identify maternal genetic risk loci for preeclampsia...
July 2012: Pregnancy Hypertension
Guillaume Desnoyers, Laura D Frost, Lynn Courteau, Michael L Wall, Stephen M Lewis
UNLABELLED: The eIF3e protein is a component of the multisubunit eIF3 complex, which is essential for cap-dependent translation initiation. Decreased eIF3e expression is often observed in breast and lung cancer and has been shown to induce epithelial-to-mesenchymal transition (EMT) in breast epithelial cells by an unknown mechanism. Here, we study the effect of decreased eIF3e expression in lung epithelial cells by creating stable clones of lung epithelial cells (A549) that express an eIF3e-targeting shRNA...
October 2015: Molecular Cancer Research: MCR
Joanna Domagala-Kulawik
Over a hundred years after the first description of this disease, lung cancer represents one of the major challenges in oncology. Radical treatment cannot be introduced in more than 70% of cases and overall survival rate does not exceed 15%. The immunosurveillance of lung cancer may be effective in early oncogenesis but is inhibited in the course of developing a clinically detectable tumor. Very low and heterogonous antigenicity of lung cancer cells leads to passive escape from anti-cancer immune defense. The cytotoxic lymphocytes (CTLs) that play a main role in the anticancer response are actively suppressed in the tumor environment and following regulatory mechanisms inhibit the recognition of tumor antigens by antigen presenting cells...
April 2015: Translational Lung Cancer Research
Shisuo Du, Sophie Bouquet, Chen-Hao Lo, Ilenia Pellicciotta, Shiva Bolourchi, Renate Parry, Mary Helen Barcellos-Hoff
PURPOSE: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non-small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. METHODS AND MATERIALS: TGF-β-mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure...
January 1, 2015: International Journal of Radiation Oncology, Biology, Physics
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