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Igf signaling

Suraiya Haroon, Annie Li, Jaye L Weinert, Clark Fritsch, Nolan G Ericson, Jasmine Alexander-Floyd, Bart P Braeckman, Cole M Haynes, Jason H Bielas, Tali Gidalevitz, Marc Vermulst
Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan...
March 20, 2018: Cell Reports
Yingying Meng, Jing Zhang, Cong Yuan, Fenglin Zhang, Qin Fu, Han Su, Xiaotong Zhu, Lina Wang, Ping Gao, Gang Shu, Qingyan Jiang, Songbo Wang
This study aimed to investigate the effects of oleic acid (OA), a monounsaturated fatty acid, on HC11 mammary epithelial cells proliferation and peripubertal mammary gland development and explore the underlying mechanisms. HC11 cells and C57BL/6J mice were treated with OA. HC11 proliferation, peripubertal mammary gland development, and the involvement of CD36 and PI3K/Akt were assessed. In vitro , 100 μM OA significantly promoted HC11 proliferation by increasing Cyclin D1/3 and PCNA expression and decreasing p21 expression...
February 27, 2018: Oncotarget
Po-Chen Chu, Peng-Chan Lin, Hsing-Yu Wu, Kuen-Tyng Lin, Christina Wu, Tanios Bekaii-Saab, Yih-Jyh Lin, Chung-Ta Lee, Jeng-Chang Lee, Ching-Shih Chen
Although the role of insulin-like growth factor-I receptor (IGF-IR) in promoting colorectal liver metastasis is known, the mechanism by which IGF-IR is upregulated in colorectal cancer (CRC) is not defined. In this study, we obtained evidence that mutant KRAS transcriptionally activates IGF-IR gene expression through Y-box-binding protein (YB)-1 upregulation via a novel MEK-Sp1-DNMT1-miR-137 pathway in CRC cells. The mechanistic link between the tumor suppressive miR-137 and the translational regulation of YB-1 is intriguing because epigenetic silencing of miR-137 represents an early event in colorectal carcinogenesis due to promoter hypermethylation...
March 21, 2018: Oncogene
Quanwei Zhang, Qi Wang, Jishang Gong, Jiaxing Du, Yong Zhang, Xingxu Zhao
Insulin-like growth factor 2 (IGF2) recapitulates many of the activities of insulin and promotes differentiation of myoblasts and osteoblasts, which likely contribute to genetic variations of growth potential. However, little is known about the functions and signaling properties of IGF2 variants in yaks. The over-expression vector and knockdown sequence of yak IGF2 were transfected into yak fibroblasts, and the effects were detected by a series of assays. IGF2 expression in yak muscle tissues was significantly lower than that of other tissues...
March 20, 2018: Genes
Huanhuan Luo, Fang Zhao, Fengxue Zhang, Ni Liu
The aim of the present study was to elucidate the mechanism of amygdalin treatment on reducing liver fibrosis by investigating its role in regulating the expression level of platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and PDGF receptor (PDGFR) in the hepatic stellate cell (HSC)-T6 line. HSC-T6 cells were used as an in vitro model and randomly assigned into four groups: control, high-dose amygdalin, mid-dose amygdalin and low-dose amygdalin. Following amygdalin treatment, compared with the control, a high dose of amygdalin significantly suppressed the mRNA expression of PDGF and IGF (each P<0...
April 2018: Experimental and Therapeutic Medicine
Steven A Rosenzweig
Resistance to chemotherapeutic drugs exemplifies the greatest hindrance to effective treatment of cancer patients. The molecular mechanisms responsible have been investigated for over 50 years and have revealed the lack of a single cause, but instead, multiple mechanisms including induced expression of membrane transporters that pump drugs out of cells (multidrug resistance (MDR) phenotype), changes in the glutathione system, and altered metabolism. Treatment of cancer patients/cancer cells with chemotherapeutic agents and/or molecularly targeted drugs is accompanied by acquisition of resistance to the treatment administered...
2018: Advances in Cancer Research
Atefeh Rabiee, Marcus Krüger, Jacob Ardenkjær-Larsen, C Ronald Kahn, Brice Emanuelli
Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type, IRS-1-/- and IRS-2-/- mice in the basal and IGF-1-stimulated states...
March 14, 2018: Cellular Signalling
Adam J Camblin, Emily A Pace, Sharlene Adams, Michael D Curley, Victoria Rimkunas, Lin Nie, Gege Tan, Troy Bloom, Sergio Iadevaia, Jason Baum, Charlene Minx, Akos Czibere, Chrystal U Louis, Daryl C Drummond, Ulrik B Nielsen, Birgit Schoeberl, J Marc Pipas, Robert M Straubinger, Vasileios Askoxylakis, Alexey A Lugovskoy
PURPOSE: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Charles Cai, Taimur Ahmad, Gloria B Valencia, Jacob V Aranda, Jiliu Xu, Kay D Beharry
OBJECTIVES: Extremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis...
March 8, 2018: Growth Hormone & IGF Research
Joanna Stanicka, Leonie Rieger, Sandra O'Shea, Orla Cox, Michael Coleman, Ciara O'Flanagan, Barbara Addario, Nuala McCabe, Richard Kennedy, Rosemary O'Connor
IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown. Here we investigated the non-receptor tyrosine adhesion kinase FES-related (FER), following its identification as a potential mediator of sensitivity to IGF-1R kinase inhibition in a functional siRNA screen. We found that FER and the IGF-1R co-locate in cells and can be co-immunoprecipitated. Ectopic FER expression strongly enhanced IGF-1R expression and phosphorylation on tyrosines 950 and 1131...
March 15, 2018: Oncogene
Julien Daubriac, Shiwei Han, Jelena Grahovac, Eve Smith, Abdel Hosein, Marguerite Buchanan, Mark Basik, Yves Boucher
Carcinoma-associated fibroblasts (CAFs) can remodel the extracellular matrix to promote cancer cell invasion, but the paracrine signaling between CAFs and cancer cells that regulates tumor cell migration remains to be identified. To determine how the interaction between CAFs and cancer cells modulates the invasiveness of cancer cells, we developed a 3-dimensional co-culture model composed of breast cancer (BC) MDA-MB-231 cell spheroids embedded in a collagen gel with and without CAFs. We found that the crosstalk between CAFs and cancer cells promotes invasion by stimulating the scattering of MDA-MB-231 cells, which was dependent on RhoA/ROCK/phospho MLC signaling in cancer cells but independent of RhoA in CAFs...
February 13, 2018: Oncotarget
Emilie Clement, Hiroyuki Inuzuka, Naoe T Nihira, Wenyi Wei, Alex Toker
The PI3K-AKT kinase signaling pathway is frequently deregulated in human cancers, particularly breast cancer, where amplification and somatic mutations of PIK3CA occur with high frequency in patients. Numerous small-molecule inhibitors targeting both PI3K and AKT are under clinical evaluation, but dose-limiting toxicities and the emergence of resistance limit therapeutic efficacy. Various resistance mechanisms to PI3K inhibitors have been identified, including de novo mutations, feedback activation of AKT, or cross-talk pathways...
March 13, 2018: Science Signaling
Fumihiko Hakuno, Shin-Ichiro Takahashi
Insulin-like growth factors (IGFs) bind specifically to the IGF-I receptor on the cell surface of targeted tissues. Ligand binding to the α subunit of the receptor leads to a conformational change in the β subunit, resulting in the activation of receptor tyrosine kinase activity. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src-homology collagen (Shc). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain containing signaling molecules...
March 13, 2018: Journal of Molecular Endocrinology
Rossella Titone, Meifang Zhu, Danielle M Robertson
Insulin and insulin-like growth factor-1 (IGF-1) are present in human tears and likely play an important role in mediating ocular surface homeostasis. We previously characterized the IGF-1/insulin hybrid receptor (Hybrid-R) in corneal epithelial cells and found that it was activated by IGF-1 and not insulin; and reported the novel finding that it localized to the corneal epithelial cell nucleus. Since the corneal epithelium is an insulin insensitive tissue and does not require insulin for glucose uptake, this study investigated the function of insulin in corneal epithelial cells...
March 12, 2018: Scientific Reports
Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner, Alan M Fogelman, Srinivasa T Reddy
Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue...
March 12, 2018: Cell Death & Disease
Debarati Chattopadhyay, Kavitha Thirumurugan
Past investigations have shown that various plant extracts are capable of promoting longevity in lower model organisms like Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Bombyx mori etc. Longevity studies on such organisms provide a foundation to explore anti-aging efficacies of such plant extracts in higher organisms. Plant extracts of acai palm, apple, asparagus, blueberry, cinnamon, cocoa, Damnacanthus, maize, mistletoe, peach, pomegranate, Rhodiola, rose, Sasa, turmeric, and Withania have extended lifespan in lower model organisms via diverse mechanisms like insulin like growth factor (IGF) signaling pathway, and antioxidant defense mechanisms...
March 8, 2018: Mechanisms of Ageing and Development
Lin Zhou, Lu Wang, Shuju Bai, Shu Xing, Wannan Li, Junfeng Ma, Xueqi Fu
Low molecular weight protein tyrosine phosphatase (LMW-PTP) is highly conserved across almost all living organisms and is involved in the modulation of a number of cellular proteins related to important signaling pathways. In this study, we isolated lmwptp (Y94H6A.7) of Caenorhabditis elegans, the homolog of human ACP1, and set up an effective feeding-based RNA interference (RNAi) knockdown against this gene. We found that knockdown of lmwptp decreased damage associated with heat shock, oxidative stress and UV irradiation in wild-type worms, however, its deficiency didn't further reduce the stress resistance of hsf-1 or daf-16 mutants and didn't further increase the stress sensitivity associated with age-1, akt-1 or akt-2 mutants, but it enhanced the stress resistance of daf-2 mutants...
March 7, 2018: International Journal of Biological Macromolecules
Jingwen Liao, Yanyan Zhang, Ying Wu, Fanxing Zeng, Lijun Shi
AIMS: This study investigated whether long-term exercise can influence vascular smooth muscle cells (VSMCs) phenotypic switching in mesenteric arteries of hypertensive rats, with a focus on the modulation of protein kinase B (PKB/Akt) signaling by microRNA-145 (miR-145). MAIN METHODS: In the exercise intervention experiment, mesenteric arteries from 3-month-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were isolated for histological observation, phenotypic marker analysis, Akt phosphorylation quantification, and miR-145 evaluation after being subjected to moderate-intensity treadmill training (E) or being sedentary (C) for 8 weeks...
March 6, 2018: Life Sciences
Lei Wang, Mengnan Yang, Minfei Jin, Yuelin Wu, Tao Zheng, Shengyi Gu, Xiaolin Hua
To investigate the potential beneficial effect of insulin-like growth factor-1 (IGF-1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF-1 and IL-10 were determined by RT-PCR and immunoblotting. The secretory IL-10 and released E2 were measured using ELISA kits. The relative vWF and α-SMA expressions were determined by immunohistochemistry. The direct binding of NF-κB subunit p50 with IL-10 promoter was analysed by chromatin immunoprecipitation assay...
March 7, 2018: Journal of Cellular and Molecular Medicine
Liying Yang, Hongyan Wang, Lijun Liu, Anmu Xie
Dementia, a condition that frequently afflicts patients in advanced stages of Parkinson's disease (PD), results in decreased quality of life and survival time. Nevertheless, the pathological mechanisms underlying Parkinson's disease dementia (PDD) are not completely understood. The symptoms characteristic of PDD may be the result of functional and structural deficiencies. The present study implicates the accumulation of Lewy bodies in the cortex and limbic system as a potent trigger in the development of PDD...
2018: Frontiers in Neuroscience
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