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PI3k lung

Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
Fazeela Mahaboob Begum S M, Kalai Chitra, Benin Joseph, Raji Sundararajan, Hemalatha S
BACKGROUND: Lung adenocarcinoma is the most common subtype of Non small cell lung cancer in which the PI3K/Akt cascade is frequently deregulated. The ubiquitous expression of the PI3K and the frequent inactivation of PTEN accounts for the prolonged survival, evasion of apoptosis and metastasis in cancer. This has led to the development of PI3K inhibitors in the treatment of cancer. Synthetic PI3K inhibitors undergoing clinical and preclinical studies are toxic in animals. Hence, there is a critical need to identify PI3K inhibitor(s) of natural origin...
March 20, 2018: BMC Complementary and Alternative Medicine
Flora Pirozzi, Kai Ren, Alessandra Murabito, Alessandra Ghigo
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible chronic inflammation and airflow obstruction. It affects more than 64 million patients worldwide and it is predicted to become the third cause of death in the industrialized world by 2030. Current available therapies are not able to block disease progression and to reduce mortality, underlying the need of a better understanding of COPD pathophysiological mechanisms to identify new molecular therapeutic targets...
March 20, 2018: Current Medicinal Chemistry
Hitendra S Solanki, Remya Raja, Alex Zhavoronkov, Ivan V Ozerov, Artem V Artemov, Jayshree Advani, Aneesha Radhakrishnan, Niraj Babu, Vinuth N Puttamallesh, Nazia Syed, Vishalakshi Nanjappa, Tejaswini Subbannayya, Nandini A Sahasrabuddhe, Arun H Patil, T S Keshava Prasad, Daria Gaykalova, Xiaofei Chang, Rachana Sathyendran, Premendu Prakash Mathur, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Evgeny Izumchenko, Harsha Gowda, Aditi Chatterjee
EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells. SILAC-based mass-spectrometry approach was used to study altered signaling in H358-S cell line. Importantly, among the top phosphosites in H358-S cells we observed hyperphosphorylation of EGFR (Y1197) and non-receptor tyrosine kinase FAK (Y576/577)...
January 2018: Oncoscience
Wei Chen, Xiaoqun Liu, Sujuan Yuan, Tiankui Qiao
Although cisplatin (CDDP) is widely used for non-small-cell lung cancer (NSCLC) treatment, resistance remains a major problem that restricts its efficacy. Therefore, identification of drugs that reverse or prevent resistance to CDDP in NSCLC has been a focus of a number of studies. The results of the present study revealed the effect of heat shock protein family A member 12B (HSPA12B) overexpression on chemoresistance in A549 cells in vitro . The effect of HSPA12B overexpression on chemoresistance in mice bearing A549 xenografted tumors was then determined via stable HSPA12B transfection...
March 2018: Oncology Letters
Cheng Fu, Jie Luo, Shaotang Ye, Ziguo Yuan, Shoujun Li
Avian-like H5N1 canine influenza virus (CIV) causes severe respiratory infections in dogs. However, the mechanism underlying H5N1 CIV infection in dogs is unknown. The present study aimed to identify differentially expressed miRNAs and mRNAs in the lungs and trachea in H5N1 CIV-infected dogs through a next-generation sequencing-based method. Eighteen 40-day-old beagles were inoculated intranasally with CIV, A/canine/01/Guangdong/2013 (H5N1) at a tissue culture infectious dose 50 (TCID50 ) of 106 , and lung and tracheal tissues were harvested at 3 and 7 d post-inoculation...
2018: Frontiers in Microbiology
Li Huang, Meijuan Wang, Yongdong Yan, Wenjing Gu, Xinxing Zhang, Jiahong Tan, Huiming Sun, Wei Ji, Zhengrong Chen
BACKGROUND: The aim of this study was to investigate the mechanisms of OX40L in regulating helper T (Th) cells differentiation through phosphoinositide 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase signaling pathway in vitro and in vivo experiments. METHODS: Serum samples of patients with asthma and healthy controls were used to explore the association between OX40L and Th cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of OX40L, IL-4, IFN-γ, IL-17 and TGF-β...
March 20, 2018: Journal of Translational Medicine
Ke-Wang Luo, Wing-Yin Lung, Chun-Xie, Xin-Le Luo, Wei-Ren Huang
Epigallocatechin-3-gallate (EGCG), the bioactive polyphenol in green tea, has been demonstrated to have various biological activities. We previously found that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9. This study demonstrated that EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway, without modulation of NF-κB. Our results showed that treatment of EGCG resulted in significant inhibition of cell proliferation by induction of apoptosis, without obvious toxicity to normal bladder SV-HUC-1 cells...
February 23, 2018: Oncotarget
Xuelian Xiao, Daheng Yang, Xue Gong, Dongping Mo, Shiyang Pan, Jian Xu
miRNAs play important roles in lung adenocarcioma (LADC) progression. We previously found that miR-1290 expression was upregulated in LADC tissue and serum samples from patients with LADC, and correlated with prognosis. However, the biological role of miR-1290 in LADC and mechanism of such role are poorly understood. Here, we found that miR-1290 overexpression promoted LADC cell proliferation, cell cycle progression and invasion, while suppressing cell apoptosis in vitro . Furthermore, miR-1290 promoted tumor growth, invasion and metastasis in vivo ...
February 23, 2018: Oncotarget
Suolin Zhang, Yayan Wang
Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated...
April 2018: Oncology Letters
Qianqian Wang, Jiahui Xu, Ying Li, Jumin Huang, Zebo Jiang, Yuwei Wang, Liang Liu, Elaine Lai Han Leung, Xiaojun Yao
Protein arginine methyltransferase 5 (PRMT5) is able to regulate gene transcription by catalyzing the symmetrical dimethylation of arginine residue of histone, which plays a key role in tumorigenesis. Many efforts have been taken in discovering small-molecular inhibitors against PRMT5, but very few were reported and most of them were SAM-competitive. EPZ015666 is a recently reported PRMT5 inhibitor with a new binding site, which is different from S-adenosylmethionine (SAM)-binding pocket. This new binding site provides a new clue for the design and discovery of potent and specific PRMT5 inhibitors...
2018: Frontiers in Pharmacology
Qianjin Li, Omar Awad Alsaidan, Yongjie Ma, Sungjin Kim, Junchen Liu, Thomas Albers, Kebin Liu, Zanna Beharry, Shaying Zhao, Fen Wang, Iryna Lebedyeva, Houjian Cai
Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling facilitates tumor initiation and progression. Although currently approved inhibitors of FGFR kinase have shown therapeutic benefit in clinical trials, over-expression or mutations of FGFRs eventually confer drug resistance and thereby abrogate the desired activity of kinase inhibitors in many cancer types. In this study, we report that loss of myristoylation of fibroblast growth factor receptor substrate 2 (FRS2α), a scaffold protein essential for FGFR signaling, inhibits FGF/FGFR-mediated oncogenic signaling and FGF10-induced tumorigenesis...
March 14, 2018: Journal of Biological Chemistry
Shaohui Wang, Yu Yan, Zhekang Cheng, Yanlan Hu, Tongxiang Liu
Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and metastasis, and offers insight into novel strategies for cancer treatment. Sotetsuflavone was isolated from Cycas revolute , which has excellent anticancer activity in the early stages. The present study aims to evaluate the anti-metastatic potential of sotetsuflavone in vitro. Our data demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and EMT. This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail...
December 2018: Cell Death Discovery
Sarah A Best, David P De Souza, Ariena Kersbergen, Antonia N Policheni, Saravanan Dayalan, Dedreia Tull, Vivek Rathi, Daniel H Gray, Matthew E Ritchie, Malcolm J McConville, Kate D Sutherland
The lung presents a highly oxidative environment, which is tolerated through engagement of tightly controlled stress response pathways. A critical stress response mediator is the transcription factor nuclear factor erythroid-2-related factor 2 (NFE2L2/NRF2), which is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1). Alterations in the KEAP1/NRF2 pathway have been identified in 23% of lung adenocarcinomas, suggesting that deregulation of the pathway is a major cancer driver. We demonstrate that inactivation of Keap1 and Pten in the mouse lung promotes adenocarcinoma formation...
March 2, 2018: Cell Metabolism
Lin Wang, Lin Shi, Jie Gu, Cheng Zhan, Junjie Xi, Jianyong Ding, Di Ge
Epithelial neutrophil-activating peptide-78 (CXCL5), a member of the subgroup of CXC-type chemokine family, is an inflammatory factor involved in the progression of lung cancer, but the underlying mechanism remains unclear. In this study, we investigated the effects of CXCL5 on proliferation and migration in non-small cell lung cancer (NSCLC) using tissue microarrays from NSCLC patients and H460 cells transfected with a CXCL5-interfered lentivirus vector or stimulated with recombinant CXCL5. We observed that the expression of CXCL5 was significantly higher in lung cancer cell lines, and high CXCL5 was associated with high chemokine (C-X-C motif) receptor 2 expression and was significantly associated with poor differentiation...
March 10, 2018: Journal of Physiology and Biochemistry
Risa Akizuki, Ryohei Maruhashi, Hiroaki Eguchi, Kazuki Kitabatake, Mitsutoshi Tsukimoto, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells...
March 7, 2018: Biochimica et Biophysica Acta
Xianhua Gui, Lingyun Sun, Luo Gu, Hourong Cai, Hongwei Chen
Leptin, a protein-related product of the obesity gene, plays an important role in the pathogenesis of fibrotic diseases including pulmonary fibrosis. As a highly conservative process, autophagy regulates various biological functions. Otherwise, insufficient autophagy has been described in alveolar epithelial cells (AEC) to cope with the progression of pulmonary fibrosis. Hence, this study is to investigate the effects of leptin on fibrosis in TGF-β1 induced epithelial mesenchymal transition (EMT) and the potential roles of autophagy in this processes...
March 7, 2018: Biochemical and Biophysical Research Communications
Jianhua Zhu, Jianfeng Yao, Rongfu Huang, Yueqin Wang, Min Jia, Yan Huang
Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the resent study, we explored the role of ghrelin in A549 cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549 cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549 cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K...
March 7, 2018: Biochemical and Biophysical Research Communications
Clare A Stokes, Alison M Condliffe
Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders...
March 9, 2018: Biochemical Society Transactions
Eunjung Kim, Jae-Young Kim, Matthew A Smith, Eric B Haura, Alexander R A Anderson
During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway...
March 2018: PLoS Biology
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