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IGF1R cancer

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https://www.readbyqxmd.com/read/28613101/targeting-igf1r-pathway-in-cancer-with-micrornas-how-close-are-we
#1
Arathy S Kumar, Suresh K Rayala, Ganesh Venkatraman
Cancer of the head and neck are the most common cancers in India and account for 30% of all cancers. At molecular level, it could be attributed to the over-expression of growth factors like IGF1-R, EGFR, VEGF-R and deregulation of cell cycle regulators and tumor suppressors. IGF1-R is an emerging target in head and neck cancer treatment, because of its reported role in tumor development, progression and metastasis. IGF1R targeted agents are in advanced stages of clinical development. Nevertheless, these agents suffer from several disadvantages including acquired resistance and toxic side effects...
June 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28599664/angiotensin-ii-type-2-receptor-promotes-apoptosis-and-inhibits-angiogenesis-in-bladder-cancer
#2
Nana Pei, Yingying Mao, Pengfei Wan, Xinglu Chen, Andrew Li, Huiying Chen, Jinlong Li, Renqiang Wan, Yanling Zhang, Hongyan Du, Baihong Chen, Guangyu Jiang, Minghan Xia, Colin Sumners, Guixue Hu, Dongsheng Gu, Hongwei Li
BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs. RESULTS: In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated...
June 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#3
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#4
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571043/microrna-7-suppresses-the-homing-and-migration-potential-of-human-endothelial-cells-to-highly-metastatic-human-breast-cancer-cells
#5
Yu-Xin Cui, Robyn Bradbury, Valentina Flamini, Bo Wu, Nicola Jordan, Wen G Jiang
BACKGROUND: MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells. METHODS: Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays...
June 1, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#6
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533226/igf1r-protein-expression-is-not-associated-with-differential-benefit-to-concurrent-trastuzumab-in-early-stage-her2-breast-cancer-from-the-north-central-cancer-treatment-group-alliance-adjuvant-trastuzumab-trial-n9831
#7
Monica M Reinholz, Beiyun Chen, Amylou C Dueck, Kathleen Tenner, Karla Ballman, Darren Riehle, Robert B Jenkins, Xochiquetzal J Geiger, Ann E McCullough, Edith A Perez
Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2(+) adjuvant N9831 trial...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28528691/the-igf-axis-in-hpv-associated-cancers
#8
REVIEW
Adam Pickard, Julia Durzynska, Dennis J McCance, Elisabeth R Barton
Human papillomaviruses (HPV) infect and replicate in stratified epithelium at cutaneous and mucosal surfaces. The proliferation and maintenance of keratinocytes, the cells which make up this epithelium, are controlled by a number of growth factor receptors such as the keratinocyte growth factor receptor (KGFR, also called fibroblast growth factor receptor 2b (FGFR2b)), the epithelial growth factor receptor (EGFR) and the insulin-like growth factor receptors 1 and 2 (IGF1R and IGF2R). In this review, we will delineate the mutation, gene transcription, translation and processing of the IGF axis within HPV associated cancers...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28521298/insulin-like-growth-factor-2-axis-supports-the-serum-independent-growth-of-malignant-rhabdoid-tumor-and-is-activated-by-microenvironment-stress
#9
Ting Li, Jin Wang, Pengfei Liu, Jiadong Chi, Han Yan, Lei Lei, Zexing Li, Bing Yang, Xi Wang
Malignant rhabdoid tumors (MRTs) are rare, lethal, pediatric tumors predominantly found in the kidney, brain and soft tissues. MRTs are driven by loss of tumor suppressor SNF5/INI1/SMARCB1/BAF47. The prognosis of MRT is poor using currently available treatments, so new treatment targets need to be identified to expand treatment options for patients experiencing chemotherapy resistance. The growth hormone insulin-like growth factor 2 (IGF2) signaling pathway is a promising target to overcome drug resistance in many cancers...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507201/sensitivity-of-non-small-cell-lung-cancer-to-erlotinib-is-regulated-by-the-notch-mir-223-fbxw7-pathway
#10
Haiwei Zhang, Fanglin Chen, Yongpeng He, Lin Yi, Chuang Ge, Xiaolong Shi, Chao Tang, Donglin Wang, Yongzhong Wu, Weiqi Nian
Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor cell sensitivity to chemotherapeutic drugs; however, its role in cellular resistance to the effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC) remains to be elucidated. The levels of miR-223 in parental cell line (HCC827) and erlotinib resistant HCC827 cell line (HCC827/ER)  were detected by qRT-PCR. HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or RO4929097 to block the Notch signaling pathway, and then transfected with a miR-223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R)...
May 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28500773/the-energy-sensing-lkb1-ampk%C3%AE-1-pathway-regulates-igf1-secretion-and-consequent-activation-of-the-igf1r-pkb-pathway-in-primary-hepatocytes
#11
Liang Chen, Qiaoli Chen, Ping Rong, Hong Yu Wang, Shuai Chen
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating of its secretion is not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and accumulative evidence shows that AMPK is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28498399/dual-inhibition-of-igf1r-and-er-enhances-response-to-trastuzumab-in-her2-positive-breast-cancer-cells
#12
Martina S J McDermott, Alexandra Canonici, Laura Ivers, Brigid C Browne, Stephen F Madden, Neil A O'Brien, John Crown, Norma O'Donovan
Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive...
April 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28468775/targeting-insulin-receptor-in-breast-cancer-using-small-engineered-protein-scaffolds
#13
Jie Ying Chan, Benjamin J Hackel, Douglas Yee
Insulin receptor (InsR) and the type I insulin-like growth factor (IGF1R) are homologous receptors necessary for signal transduction by their cognate ligands insulin, insulin-like growth factor-I and -II (IGF-I and IGF-II). IGF1R monoclonal antibodies, intended to inhibit malignant phenotypic signaling, failed to show benefit in patients with endocrine-resistant tumors in phase III clinical trials. Our previous work showed that in tamoxifen-resistant cells IGF1R expression was lacking but InsR inhibition effectively blocked growth...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#14
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
April 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#15
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28439706/cks1bp7-a-pseudogene-of-cks1b-is-co-amplified-with-igf1r-in-breast-cancers
#16
Yansong Liu, Wei Wang, Yan Li, Feifei Sun, Jiaxiang Lin, Li Li
Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes...
April 24, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28418902/igf1r-depletion-facilitates-met-amplification-as-mechanism-of-acquired-resistance-to-erlotinib-in-hcc827-nsclc-cells
#17
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resistance to EGFR-directed drugs as well as in EMT. In the present study, we have investigated the involvement of IGF1R in acquired high-dose erlotinib resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417283/bis-anthracycline-wp760-abrogates-melanoma-cell-growth-by-transcription-inhibition-p53-activation-and-igf1r-downregulation
#18
Magdalena Olbryt, Aleksandra Rusin, Izabela Fokt, Anna Habryka, Patrycja Tudrej, Sebastian Student, Aleksander Sochanik, Rafał Zieliński, Waldemar Priebe
Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations...
April 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28404630/mir-424-322-503-is-a-breast-cancer-tumor-suppressor-whose-loss-promotes-resistance-to-chemotherapy
#19
Ruth Rodriguez-Barrueco, Erin A Nekritz, François Bertucci, Jiyang Yu, Felix Sanchez-Garcia, Tizita Z Zeleke, Andrej Gorbatenko, Daniel Birnbaum, Elena Ezhkova, Carlos Cordon-Cardo, Pascal Finetti, David Llobet-Navas, Jose M Silva
The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28403518/formation-of-the-igf1r-cav1-src-tri-complex-antagonizes-trail-induced-apoptosis-in-gastric-cancer-cells
#20
Tianshu Guo, Ling Xu, Xiaofang Che, Simeng Zhang, Ce Li, Jin Wang, Jing Gong, Rui Ma, Yibo Fan, Kezuo Hou, Huiming Zhou, Xuejun Hu, Yunpeng Liu, Xiujuan Qu
Lipid rafts provide a biological platform for apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We previously reported that insulin-like growth factor 1 receptor (IGF1R) translocation into lipid rafts helped to explain TRAIL resistance. However, it was not clear whether TRAIL resistance was caused by the interaction of IGF1R with caveolin-1 (CAV1) and the non-receptor tyrosine kinase SRC in lipid rafts of gastric cancer cells. Here, we observed high IGF1R expression in TRAIL-resistant gastric cancer cells, and showed that IGF1R combined with both CAV1 and SRC in a native complex...
April 12, 2017: Cell Biology International
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