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IGF-1R

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https://www.readbyqxmd.com/read/28821609/insulin-like-growth-factor-1-signalling-is-essential-for-mitochondrial-biogenesis-and-mitophagy-in-cancer-cells
#1
Amy Lyons, Michael Coleman, Sarah Riis, Cedric Favre, Ciara H O'Flanagan, Alexander V Zhdanov, Dmitri B Papkovsky, Stephen D Hursting, Rosemary O'Connor
Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an Insulin-like Growth Factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells, and whether this contributes to therapy resistance. Here, we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#2
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28810619/microrna-503-suppresses-cell-proliferation-and-invasion-in-osteosarcoma-via-targeting-insulin-like-growth-factor-1-receptor
#3
Zili Wang, Chenhuang Zheng, Kunqi Jiang, Jinshen He, Xu Cao, Song Wu
MicroRNAs (miRs) are a class of small non-coding RNAs and have key roles in various cancer types. Recently, miR-503 has been reported to act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of the regulatory role of miR-503 in osteosarcoma cell proliferation and invasion has largely remained elusive. The present study found that miR-503 was significantly downregulated in osteosarcoma tissues compared to that in matched adjacent non-tumorous tissues. In addition, the expression of miR-503 in osteosarcoma of T3-T4 stage was significantly lower when compared with that in T1-T2 stage samples...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810236/microrna-375-inhibits-growth-and-enhances-radiosensitivity-in-oral-squamous-cell-carcinoma-by-targeting-insulin-like-growth-factor-1-receptor
#4
Bin Zhang, Ying Li, Daorong Hou, Quan Shi, Shuo Yang, Qihong Li
BACKGROUND: MicroRNAs (miRNAs) have emerged as key players in various human biological processes, including tumorigenesis. Here, we investigated the roles of miR-375 in the pathogenesis of oral squamous cell carcinoma (OSCC). METHODS: We performed quantitative real-time PCR (qRT-PCR) to detect miR-375 expression in OSCC tissues and corresponding normal oral epithelial tissues and analyze the correlation of miR-375 expression with OSCC metastasis and patient's survival...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28796787/the-quinic-acid-derivative-kz-41-prevents-glucose-induced-caspase-3-activation-in-retinal-endothelial-cells-through-an-igf-1-receptor-dependent-mechanism
#5
Hui He, Rebecca L Weir, Jordan J Toutounchian, Jayaprakash Pagadala, Jena J Steinle, Jerome Baudry, Duane D Miller, Charles R Yates
Retinal microaneurysms, an early disease manifestation of diabetic retinopathy, are associated with retinal endothelial cell (REC) death and macular edema. We previously demonstrated that a quinic acid (QA) analog, KZ-41, promoted REC survival by blunting stress-induced p38 MAPK activation. Herein, we sought to expand our understanding of the pro-survival signal transduction pathways actuated by KZ-41. Using human RECs exposed to high glucose (25 mM, 72 hours), we demonstrated that KZ-41 blocks caspase-3 activation by triggering phosphorylation of the PI3K regulatory subunit (p85; Tyr458) and its downstream target Akt (Ser473)...
2017: PloS One
https://www.readbyqxmd.com/read/28794445/igf-1-receptor-regulates-dynamic-changes-in-neuronal-polarity-during-cerebral-cortical-migration
#6
Álvaro F Nieto Guil, Mariana Oksdath, Linnea A Weiss, Diego J Grassi, Lucas J Sosa, Marta Nieto, Santiago Quiroga
During cortical development, neurons undergo polarization, oriented migration and layer-type differentiation. The biological and biochemical mechanisms underlying these processes are not completely understood. In neurons in culture we showed that IGF-1 receptor activation is important for growth cone assembly and axonal formation. However, the possible roles of the insulin like growth factor-1 receptor (IGF-1R) on neuronal differentiation and polarization in vivo in mammals have not yet been studied. Using in utero electroporation, we show here that the IGF-1R is essential for neocortical development...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753565/enhanced-response-of-melanoma-cells-to-mek-inhibitors-following-unbiased-igf-1r-down-regulation
#7
Naida Suleymanova, Caitrin Crudden, Claire Worrall, Anica Dricu, Ada Girnita, Leonard Girnita
Due to its ability to compensate for signals lost following therapeutic MAPK-inhibition, insulin-like growth factor type 1 receptor (IGF-1R) co-targeting is a rational approach for melanoma treatment. However IGF-1R conformational changes associated with its inhibition can preferentially activate MAPK-pathway in a kinase-independent manner, through a process known as biased signaling. We explored the impact of biased IGF-1R signaling, on response to MAPK inhibition in a panel of skin melanoma cell lines with differing MAPK and p53 mutation statuses...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747084/mir-615-5p-depresses-natural-killer-cells-cytotoxicity-through-repressing-igf-1r-in-hepatocellular-carcinoma-patients
#8
Mai Atef Rahmoon, Rana Ahmed Youness, Asmaa Ibrahim Gomaa, Mohamed Tarif Hamza, Imam Waked, Hend Mohamed El Tayebi, Ahmed Ihab Abdelaziz
miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56(dim), increased CD56(bright) NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins...
July 27, 2017: Growth Factors
https://www.readbyqxmd.com/read/28743112/microrna-302b-3p-suppresses-cell-proliferation-through-akt-pathway-by-targeting-igf-1r-in-human-gastric-cancer
#9
Bo Guo, Zhenghao Zhao, Zhen Wang, Qian Li, Xiaofei Wang, Wenjing Wang, Tusheng Song, Che Huang
BACKGROUND/AIMS: MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. METHODS: Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p...
July 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#10
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28731178/microrna-379-acts-as-a-tumor-suppressor-in-non-small-cell-lung-cancer-by-targeting-the-igf%C3%A2-1r-mediated-akt-and-erk-pathways
#11
Fangzheng Zhou, Long Nie, Dali Feng, Siyan Guo, Ren'na Luo
Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines...
September 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731164/active-targeting-co-delivery-system-based-on-hollow-mesoporous-silica-nanoparticles-for-antitumor-therapy-in-ovarian-cancer-stem-like-cells
#12
Xin Guo, Nan Guo, Jianwen Zhao, Yunlang Cai
The combination of nanocarriers and chemotherapy drugs can release the chemotherapy drugs to the tumor tissue, which can enhance the antitumor effect and reduce the adverse reactions at the same time. In this study, a co-delivery system based on hollow mesoporous silica nanoparticles (HMSN) was developed and characterized. We also investigated the in vitro effect of this system on CD117+CD44+A2780 cell line. HMSN was selected as the nanocarrier, with -COOH modified on the surface and doxorubicin (DOX), NVP-AEW 541 (NVP) loaded inside...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28726241/investigating-the-role-of-the-igf-axis-as-a-predictor-of-biochemical-recurrence-in-prostate-cancer-patients-post-surgery
#13
Kieran J Breen, Amanda O'Neill, Lisa Murphy, Yue Fan, Susie Boyce, Noel Fitzgerald, Emma Dorris, Lauren Brady, Stephen P Finn, Brian D Hayes, Ann Treacy, Ciara Barrett, Mardiana Abdul Aziz, Elaine W Kay, John M Fitzpatrick, R William G Watson
BACKGROUND: Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery...
July 20, 2017: Prostate
https://www.readbyqxmd.com/read/28724578/induction-of-regulatory-t-cells-and-its-regulation-with-insulin-like-growth-factor-insulin-like-growth-factor-binding-protein-4-by-human-mesenchymal-stem-cells
#14
Ippei Miyagawa, Shingo Nakayamada, Kazuhisa Nakano, Kaoru Yamagata, Kei Sakata, Kunihiro Yamaoka, Yoshiya Tanaka
Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4(+) T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4(+) T cells and surface molecule expression on CD4(+) T cells were evaluated...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#15
Wei Cheng, Po-Chun Huang, Hsiao-Mei Chao, Yung-Ming Jeng, Hey-Chi Hsu, Hung-Wei Pan, Wuh-Liang Hwu, Yu-May Lee
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28716107/biomarkers-of-resistance-to-radiation-therapy-a-prospective-study-in-cervical-carcinoma
#16
P Moreno-Acosta, A Vallard, S Carrillo, O Gamboa, A Romero-Rojas, M Molano, J Acosta, D Mayorga, C Rancoule, M A Garcia, M Cotes Mestre, N Magné
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation...
July 17, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28714005/microrna%C3%A2-455-is-downregulated-in-gastric-cancer-and-inhibits-cell-proliferation-migration-and-invasion-via-targeting-insulin%C3%A2-like-growth-factor-1-receptor
#17
Shan Zhang, Wan-Ling Yin, Xin Zhang, Xiao-Yu Zhang
Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA‑455 (miR‑455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR‑455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#18
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709872/s-nitrosylation-of-the-igf-1-receptor-disrupts-the-cell-proliferative-action-of-igf-1
#19
Kazushi Okada, Bao-Ting Zhu
The insulin-like growth factor 1 receptor (IGF-1R) is a disulfide-linked heterotetramer containing two α-subunits and two β-subunits. Earlier studies demonstrate that nitric oxide (NO) can adversely affect IGF-1 action in the central nervous system. It is known that NO can induce S-nitrosylation of the cysteine residues in proteins, thereby partly contributing to the regulation of protein function. In the present study, we sought to determine whether S-nitrosylation of the cysteine residues in IGF-1R is an important post-translational modification that regulates its response to IGF-1...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708941/regulation-of-the-insulin-akt-signaling-pathway-and-glycolysis-during-dehydration-stress-in-the-african-clawed-frog-xenopus-laevis
#20
Cheng-Wei Wu, Shannon N Tessier, Kenneth B Storey
Estivation is an adaptive stress response utilized by some amphibians during periods of drought in the summer season. In this study, we examine the regulation of the insulin signaling cascade and glycolysis pathway in the African clawed frog Xenopus laevis during dehydration stress induced state of estivation. We show that in the brain and heart of X. laevis, dehydration reduces the phosphorylation of the insulin growth factor-1 receptor (IGF-1R), and this is followed by similar reductions in the phosphorylation of the Akt and mechanistic target of rapamycin (mTOR) kinase...
July 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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