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IGF1R cancer

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https://www.readbyqxmd.com/read/29137348/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#1
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Siggillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29119846/carbonate-apatite-nanoparticles-carry-sirna-s-targeting-growth-factor-receptor-genes-egfr1-and-erbb2-to-regress-mouse-breast-tumor
#2
Snigdha Tiash, Nur Izyani Binti Kamaruzman, Ezharul Hoque Chowdhury
Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these cells highly express growth factor receptors (GFRs), eliciting growth, and cell division. Among the GFRs, epidermal growth factor receptor-1 (EGFR1) (Her1/ERBB1) and epidermal growth factor receptor-2 (EGFR2) (Her2/ERBB2) from epidermal growth factor (EGF) family and insulin-like growth factor-1 receptor (IGF1R) are highly expressed on breast cancer cells, thus contributing to the aggressive growth and invasiveness, have been focused in this study...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29112114/role-of-scaffold-protein-proline-glutamic-acid-and-leucine-rich-protein-1-pelp1-in-the-modulation-of-adrenocortical-cancer-cell-growth
#3
Arianna De Luca, Paola Avena, Rosa Sirianni, Adele Chimento, Francesco Fallo, Catia Pilon, Ivan Casaburi, Vincenzo Pezzi
PELP1 acts as an estrogen receptor (ER) coactivator that exerts an essential role in the ER's functions. ER coregulators have a critical role in the progression and response to hormonal treatment of estrogen-dependent tumors. We previously demonstrated that, in adrenocortical carcinoma (ACC), ERα is upregulated and that estradiol activates the IGF-II/IGF1R signaling pathways defining the role of this functional cross-talk in H295R ACC cell proliferation. The aim of this study was to determine if PELP1 is expressed in ACC and may play a role in promoting the interaction between ERα and IGF1R allowing the activation of pathways important for ACC cell growth...
November 7, 2017: Cells
https://www.readbyqxmd.com/read/29100507/inhibition-of-pi3k-akt-mtor-overcomes-cisplatin-resistance-in-the-triple-negative-breast-cancer-cell-line-hcc38
#4
Katharina Gohr, Alexandra Hamacher, Laura H Engelke, Matthias U Kassack
BACKGROUND: Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings. METHODS: The TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3...
November 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29099049/receptors-for-insulin-like-growth-factor-2-and-androgens-as-therapeutic-targets-in-triple-negative-breast-cancer
#5
Nalo Hamilton, David Austin, Diana Márquez-Garbán, Rudy Sanchez, Brittney Chau, Kay Foos, Yanyuan Wu, Jaydutt Vadgama, Richard Pietras
Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29069776/the-crucial-role-of-srpk1-in-igf-1-induced-emt-of-human-gastric-cancer
#6
Hong Wang, Chunlei Wang, Wenling Tian, Yanfen Yao
In recent years, the insulin-like growth factor (IGF-1) and serine-arginine protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial-mesenchymal transition (EMT) in many kinds of malignancies. However, the potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have not been investigated. In the present study, the in-vitro assays were used to investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness. We demonstrated that the expressions of SRPK1 or insulin-like growth factor receptor 1 (IGF1R) were significantly increased in GC tissues and cells than those in normal tissues and GES-1 cells, and closely associated with metastasis, stage and prognosis...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29054976/regulation-of-insulin-like-growth-factor-receptors-by-ubiquilin1
#7
Zimple Kurlawala, Rain Dunaway, Parag P Shah, Julie A Gosney, Leah J Siskind, Brian P Ceresa, Levi J Beverly
Insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase that mediates growth, proliferation and survival. Dysregulation of IGF pathway contributes to initiation, progression and metastasis of cancer and is also involved in diseases of glucose metabolism, such as Diabetes. We have identified Ubiquilin1 (UBQLN1) as a novel interaction partner of IGF1R, IGF2R and Insulin Receptor. UBQLN family of proteins have been studied primarily in the context of protein quality control and in the field of neurodegenerative disorders...
October 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29029116/upregulation-of-irs1-enhances-igf1-response-in-y537s-and-d538g-esr1-mutant-breast-cancer-cells
#8
Zheqi Li, Kevin M Levine, Amir Bahreini, Peilu Wang, David Chu, Ben Ho Park, Steffi Oesterreich, Adrian V Lee
Increased evidence suggests that somatic mutations in the ligand binding domain of estrogen receptor (ERα/ESR1) are critical mediators of endocrine-resistant breast cancer progression. Insulin-like growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis, and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29028222/role-of-rbp2-induced-er-and-igf1r-erbb-signaling-in-tamoxifen-resistance-in-breast-cancer
#9
Hee-Joo Choi, Hyeong-Seok Joo, Hee-Young Won, Kyueng-Whan Min, Hyung-Yong Kim, Taekwon Son, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong
Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764)...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29022361/interactions-of-quercetin-with-receptor-tyrosine-kinases-associated-with-human-lung-carcinoma
#10
Bincy Baby, Priya Antony, Ranjit Vijayan
Lung cancer is a deadly form of cancer with high morbidity and mortality rates. Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the formation and development of lung carcinoma. Quercetin is a major dietary flavonoid that has been shown to induce cell growth inhibition and apoptosis in human lung cancer cell lines. In the current study, four major overexpressed RTKs - EGFR, FGFR1, IGF1R and c-Met - involved in human lung cancer were investigated. Molecular docking was employed to identify the binding orientation and inhibitory potential of quercetin in these RTKs...
October 12, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28991240/polypharmacology-based-ceritinib-repurposing-using-integrated-functional-proteomics
#11
Brent M Kuenzi, Lily L Remsing Rix, Paul A Stewart, Bin Fang, Fumi Kinose, Annamarie T Bryant, Theresa A Boyle, John M Koomen, Eric B Haura, Uwe Rix
Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, here we describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identify new targets and network-wide signaling effects...
October 9, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28977934/shuanghuang-shengbai-granule-cures-myelosuppression-and-suppresses-lung-cancer-progression-mechanism-and-therapeutic-targets-from-the-aspect-of-micrornas
#12
Shuang Wang, Zhenye Xu, Lifang Wang
BACKGROUND: Shuanghuang Shengbai granule is effective in curing cyclophosphamide-induced myelosuppression without promoting lung cancer development. This study aims to investigate its mechanism and therapeutic targets. METHODS: Nude mice with lung cancer were treated with physiological saline (control), cyclophosphamide, or cyclophosphamide + Shuanghuang Shengbai. MicroRNA microarray was used to investigate the differentially expressed microRNAs in lung cancer stem cells or bone marrow hematopoietic stem cells between the three groups...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28956832/multiple-gene-environment-interactions-on-the-angiogenesis-gene-pathway-impact-rectal-cancer-risk-and-survival
#13
Noha Sharafeldin, Martha L Slattery, Qi Liu, Conrado Franco-Villalobos, Bette J Caan, John D Potter, Yutaka Yasui
Characterization of gene-environment interactions (GEIs) in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival...
September 28, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28955730/tgf-%C3%AE-stimulation-of-emt-programs-elicits-non-genomic-er-%C3%AE-activity-and-anti-estrogen-resistance-in-breast-cancer-cells
#14
Maozhen Tian, William P Schiemann
AIM: Estrogen receptor-α (ER-α) activation drives the progression of luminal breast cancers. Signaling by transforming growth factor-β (TGF-β) typically opposes the actions of ER-α; it also induces epithelial-mesenchymal transition (EMT) programs that promote breast cancer dissemination, stemness, and chemoresistance. The impact of EMT programs on nongenomic ER-α signaling remains unknown and was studied herein. METHODS: MCF-7 and BT474 cells were stimulated with TGF-β to induce EMT programs, at which point ER-α expression, localization, and nongenomic interactions with receptor tyrosine kinases and MAP kinases (MAPKs) were determined...
2017: Journal of Cancer Metastasis and Treatment
https://www.readbyqxmd.com/read/28954282/targeting-the-oncogenic-transcriptional-regulator-myb-in-adenoid-cystic-carcinoma-by-inhibition-of-igf1r-akt-signaling
#15
Mattias K Andersson, Maryam K Afshari, Ywonne Andrén, Michael J Wick, Göran Stenman
Background: Adenoid cystic carcinoma (ACC) is an aggressive cancer with no curative treatment for patients with recurrent/metastatic disease. The MYB-NFIB gene fusion is the main genomic hallmark and a potential therapeutic target. Methods: Oncogenic signaling pathways were studied in cultured cells and/or tumors from 15 ACC patients. Phospho-receptor tyrosine kinase (RTK) arrays were used to study the activity of RTKs. Effects of RTK inhibition on cell proliferation were analyzed with AlamarBlue, sphere assays, and two ACC xenograft models (n = 4-9 mice per group)...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28947975/phenformin-inhibits-growth-and-epithelial-mesenchymal-transition-of-erbb2-overexpressing-breast-cancer-cells-through-targeting-the-igf1r-pathway
#16
Zhiying Guo, Ming Zhao, Erin W Howard, Qingxia Zhao, Amanda B Parris, Zhikun Ma, Xiaohe Yang
Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation. Although the anti-cancer properties of metformin have been well-studied, reports on a more bioavailable/potent biguanide, phenformin, remain sparse. Phenformin exerts similar functional activity to metformin and has been reported to impede mammary carcinogenesis in rats. Since the effects of phenformin on specific breast cancer subtypes have not been fully explored, we used ErbB2-overexpressing breast cancer cell and animal models to test the anti-cancer potential of phenformin...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945762/nuclear-insulin-like-growth-factor-1-receptor-igf1r-displays-proliferative-and-regulatory-activities-in-non-malignant-cells
#17
Ravid Solomon-Zemler, Rive Sarfstein, Haim Werner
The insulin-like growth factor-1 receptor (IGF1R) mediates the biological actions of IGF1 and IGF2. The IGF1R is involved in both physiological and pathological activities and is usually overexpressed in most types of cancer. In addition to its classical mechanism of action, recent evidence has shown a nuclear presence of IGF1R, associated with novel genomic/transcriptional types of activities. The present study was aimed at evaluating the hypothesis that nuclear IGF1R localization is not restricted to cancer cells and might constitute a novel physiologically relevant regulatory mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#18
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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932920/microrna-30a-inhibits-colorectal-cancer-metastasis-through-down-regulation-of-type-i-insulin-like-growth-factor-receptor
#19
Y C Liu, Y R Park, S L Kim, S T Lee, S W Kim
BACKGROUND: miR-30a expression is down-regulated and regulates tumor suppressors in various cancers. AIM: We investigated the mechanisms underlying the biological role of miR-30a in CRC. METHODS: MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a...
November 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28900330/role-of-insulin-like-growth-factor-insulin-like-growth-factor-receptors-and-insulin-like-growth-factor-binding-proteins-in-ovarian-cancer
#20
REVIEW
Periyasamy Amutha, Thangarajan Rajkumar
Insulin and IGFs play an important role in cancer initiation and progression, including ovarian cancer (OC). Epithelial ovarian cancer (EOC) is the most frequent type of OC in women and it is the most lethal gynecological malignancy worldwide. Generally, insulin is associated with metabolism, whereas Insulin like growth factors (IGFs) are involved in cell proliferation. Hence, Insulin-like growth factor binding proteins (IGFBPs) determines the bioavailability of IGFs in circulation. The interplay between these molecules such as insulin, IGFs, IGFBPs and insulin-like growth factor receptor 1 (IGF1R) may be crucial for ovarian cancer cell biology and cancer progression...
April 2017: Indian Journal of Medical and Paediatric Oncology
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