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IGF1R cancer

Heleen K Bronsveld, Marie L De Bruin, Jelle Wesseling, Joyce Sanders, Ingrid Hofland, Vibeke Jensen, Marloes T Bazelier, Bas Ter Braak, Anthonius de Boer, Peter Vestergaard, Marjanka K Schmidt
BACKGROUND: The insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer. We aimed to evaluate the expression of hormone and insulin-related proteins within or related to the PI3K and MAPK pathway in breast tumors of women with or without diabetes mellitus, treated with or without insulin (analogues). METHODS: Immunohistochemistry was performed on tumor tissue of 312 women with invasive breast cancer, with or without pre-existing diabetes mellitus, diagnosed in 2000-2010, who were randomly selected from a Danish breast cancer cohort...
February 27, 2018: BMC Cancer
Haim Werner, Shilhav Meisel-Sharon, Ilan Bruchim
The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis...
February 19, 2018: Molecular Cancer
Ho Jin Lee, Phuong Chi Pham, Seung Yeob Hyun, Byungyeob Baek, Byungjin Kim, Yunha Kim, Hye-Young Min, Jeeyeon Lee, Ho-Young Lee
BACKGROUND: Both the type I insulin-like growth factor receptor (IGF1R) and Src pathways are associated with the development and progression of numerous types of human cancer, and Src activation confers resistance to anti-IGF1R therapies. Hence, targeting both IGF1R and Src concurrently is one of the main challenges in combating resistance to the currently available anti-IGF1R-based anticancer therapies. However, the enhanced toxicity from this combinatorial treatment could be one of the main hurdles for this strategy, suggesting the necessity of developing a novel strategy for co-targeting IGF1R and Src to meet an urgent clinical need...
February 19, 2018: Molecular Cancer
Zhifen Yang, Jing Zhang, Dadi Jiang, Purvesh Khatri, David E Solow-Cordero, Diego A S Toesca, Constantinos Koumenis, Nicholas C Denko, Amato J Giaccia, Quynh-Thu Le, Albert C Koong
Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases including cancer. The inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) pathway is the most evolutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1-XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which luciferase was fused in-frame with the spliced (active) form of XBP1...
February 9, 2018: Molecular Cancer Research: MCR
Yongjiang Zheng, Jiguang Bao, Qiyi Zhao, Tianshou Zhou, Xiaoqiang Sun
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas...
February 13, 2018: Molecular Cancer Therapeutics
Abhishek Kumar, Priyashree Sunita, Shivesh Jha, Shakti P Pattanayak
Breast cancer (BC) is a persistent and impulsive metabolic disorder with the highest prevalence in women, worldwide. 7,12-Dimethylbenz(a)anthracene (DMBA) is a potent polyaromatic hydrocarbon (PAH)-based carcinogen producing mammary carcinomas in rats resembling the human hormone-dependent BC. 7,8-Dihydroxycoumarin (78DC) is a coumarin derivative that possesses diversified and favorable pharmacology profile to be considered in anticancer research against various malignancies. The present study was intended to investigate the antiproliferative and chemotherapeutic potentials of 78DC (20, 40, and 80 mg/kg BW) against DMBA (20 mg in olive oil)-induced mammary carcinoma Sprague-Dawley rats...
February 12, 2018: Journal of Physiology and Biochemistry
Ying Ye, Juhua Zhuang, Guangdong Wang, Saifei He, Suiliang Zhang, Guoyu Wang, Jing Ni, Jiening Wang, Wei Xia
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC...
January 2018: Experimental and Therapeutic Medicine
Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin...
February 5, 2018: Cancer Letters
Pingzhang Chen, Yunhong Liu, Jing Zhao, Xiaojuan Pang, Peifa Zhang, Xiaohu Hou, Ping Chen, Cheng-Yi He, Zhiyong Wang, Zhi-Ying Chen
Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD3 ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro...
February 7, 2018: Biomaterials Science
Guiyi Liao, Fangmin Chen, Jinbiao Zhong, Xinan Jiang
Bladder cancer is the most frequent malignancy of the urinary tract and the seventh most common cancer worldwide. The abnormal expression of microRNAs has been frequently observed in various types of human cancers, including bladder cancer. In addition, an increasing body of evidence has demonstrated that microRNAs are potential targets for cancer diagnosis, treatments and prognosis. The aim of the present study was to investigate the expression patterns and potential roles of microRNA‑539 (miR‑539) in bladder cancer and its underlying mechanism...
January 25, 2018: Molecular Medicine Reports
Lucy Ireland, Almudena Santos, Fiona Campbell, Carlos Figueiredo, Dean Hammond, Lesley G Ellies, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder, Michael Schmid, Ainhoa Mielgo
Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors...
January 25, 2018: Oncogene
Cecilia Rodriguez-Monterrosas, Ricardo Diaz-Aragon, Pedro Cortes-Reynosa, Eduardo Perez Salazar
Epidemiological studies and animal models suggest a link between high levels of dietary fat intake and an increased risk of developing breast cancer. Hyperinsulinemia is a feature of obesity, diabetes, and metabolic syndrome that is associated with an increased breast cancer risk. Insulin is a hormone involved in metabolic regulation of carbohydrate. However, it is also a growth factor that mediates proliferation and migration. Linoleic acid (LA) is a fatty acid that induces migration and invasion in breast cancer cells...
January 24, 2018: Journal of Cellular Biochemistry
Yinghui Zhang, Lynn Wester, Jichao He, Tamar Geiger, Marja Moerkens, Ram Siddappa, Jean A Helmijr, Mieke M Timmermans, Maxime P Look, Caroline H M van Deurzen, John W M Martens, Chantal Pont, Marjo de Graauw, Erik H J Danen, Els M J J Berns, John H N Meerman, Maurice P H M Jansen, Bob van de Water
Antiestrogen resistance in estrogen receptor positive (ER+) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of IGF1R-mediated antiestrogen with clinical significance. These include the tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21-activated kinase 2, PAK2, is the strongest resistance inducer...
January 22, 2018: Oncogene
Karthik Nagaraj, Lena Lapkina-Gendler, Rive Sarfstein, David Gurwitz, Metsada Pasmanik-Chor, Zvi Laron, Shoshana Yakar, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
Jingci Chen, Alison M Nagle, Yu-Fen Wang, David N Boone, Adrian V Lee
Breast cancer development and progression is influenced by insulin-like growth factor 1 (IGF1R) and insulin receptor (InsR) signaling that drive cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and InsR form IGF1R/InsR hybrid receptors (HybR) consisting of one molecule of IGF1R and one molecule of InsR. The specific signaling and functions of HybR are largely unknown as HybR is activated by both IGF1 and insulin, and no cellular system expresses HybR in the absence of holo-IGF1R or holo-InsR...
January 12, 2018: Journal of Biological Chemistry
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
Ferenc Sipos, Hajnal Székely, Imre Dániel Kis, Zsolt Tulassay, Györgyi Műzes
Metabolic syndrome (MetS), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor (IGF1R) signaling pathway. The IGF1R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from MetS who are at increased risk of colorectal cancer...
December 14, 2017: World Journal of Gastroenterology: WJG
Jingsheng Yuan, Zhijie Yin, Kaixiong Tao, Guobing Wang, Jinbo Gao
Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor...
January 2018: Oncology Letters
Juan Du, Yu Yu, Jun Zhan, Hongquan Zhang
Breast cancer is the most prevalent female malignancy throughout the world. Conventional treatment strategies for breast cancer consist of chemotherapy, radiation, surgery, chemoradiation, hormone therapy, and targeted therapies. Among them, targeted therapies show advantages to reduce cost and toxicity for being possible for individualized treatments based on the intrinsic subtypes of breast cancer. With deeper understanding of key signaling pathways concerning tumor growth and survival, growth factor-controlled signaling pathways are frequently dysregulated in the development and progression of breast cancer...
2017: Advances in Experimental Medicine and Biology
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