Note | |
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Entity | Breast cancer |
Note | Jackson and colleagues (Jackson, et al. 1998) observed that IRS2 is widely expressed in breast cancer cell lines and primary breast cancer cells. In breast cancer patients, membrane localization of IRS-2 was associated with reduced overall survival by multivariate analysis (Clark, et al. 2011). In breast cancer cell lines, high IRS2 expression was correlated with high breast tumor invasiveness (Porter, et al. 2013), and with increased survival and cell invasion under hypoxia conditions (Mardilovich, et al. 2009b). Breast cancer IRS2-depleted cells, using specific anti-sense constructs, presented reduced IGF1-mediated cell motility and lower anchorage independent growth (Jackson, et al. 2001). In agreement, others studies demonstrated that IRS2 activation was required for IGF1-induced cell motility of the human breast cell lines MCF-7 (Ibrahim, et al. 2008; Zhang, et al. 2004) and T47D-YA(Byron, et al. 2006). Nagle and colleagues (Nagle, et al. 2004), showed that mammary tumor cells from IRS2 knockout mice were less invasive and presented more prominent apoptotic response to growth factor deprivation compared to wild type mammary tumor cells. Using breast cancer cell lines, Morelli and colleagues (Morelli, et al. 2003) and Cui and colleagues (Cui, et al. 2003) also observed that IRS2 could be a target of estrogen and progesterone receptors, respectively. Cui and colleagues (Cui, et al. 2006) demonstrated that EGF signaling was also involved in IRS2 induction/activation at the mRNA and protein levels via c-JUN/AP-1 stimulation, establishing cross-talk between IGF1R and EGFR signaling. Furthermore, the authors demonstrated in their study that IRS2 silencing reduced EGF-induced invasion and migration in the mammary adenocarcinoma cell line MDA-MB-468 (Cui, et al. 2006). Using the nontumorigenic mammary epithelial cell line MCF-10A and transgenic mice overexpressing human IRS2 by MMTV promoter, Death and colleagues (Dearth, et al. 2006) demonstrated the potential of malignant transformation of mammary cells by in vitro and in vivo IRS2 overexpression. Wu and colleagues (Wu, et al. 2010) observed that IRS2 silencing impaired breast cancer cell proliferation. In addition, they described that IGF1 induced nuclear translocation of IRS2 and NFKB, and promoted intranuclear association between IRS2 and NFKB in MCF-7 and BT-20 breast cancer cells, establishing a cross-talk between IGF1R and NFKB signaling. Slattery and colleagues (Slattery, et al. 2007), using a cohort of 1664 patients with breast cancer (1089 non-Hispanic white and 575 Hispanic) and 2054 controls (1328 non-Hispanic white and 726 Hispanic), found no association between IRS2 G1057D (rs1805097) polymorphism and breast cancer development. In contrast, Feigelson and colleagues (Feigelson, et al. 2008) observed an association between IRS2 polymorphisms rs4773082 (640 patients and 650 controls), rs2289046 (552 patients and 589 controls) and rs754204 (642 patients and 655 controls) and breast cancer development. |
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Entity | Colorectal cancer |
Note | Slattery and colleagues (Slattery, et al. 2004), using a cohort of 1001 patients with colon cancer and 1167 controls, and 766 patients with rectal cancer and 983 controls, reported that IRS2 G1057D (rs1805097) heterozygote GD genotype significantly reduced the risk of colon, though not rectal, cancer. In contrast, Yukseloglu and colleagues (Yukseloglu, et al. 2014), observed no association between IRS2 G1057D (rs1805097) polymorphism and risk for disease in a group of 161 patients with colorectal cancer and 197 controls. Gunter and colleagues (Gunter, et al. 2007) observed no association of IRS2 polymorphisms rs2241745 (754 patients and 765 controls) and rs2289046 (744 patients and 758 controls) with advanced colorectal adenoma. IRS2 (rs2289046) GG genotype compared with AA plus AG genotypes was found to have a protective factor for colorectal cancer risk in normal weight subjects (Karimi, et al. 2013). Day and colleagues (Day, et al. 2013) described that IRS2 mRNA and protein levels were positively correlated with progression from normal through adenoma to carcinoma in colorectal cancer, and that deregulated IRS2 expression activated the PI3K/AKT pathway and increased cell adhesion. Using FISH analysis, Huang and colleagues (Huang, et al. 2015) demonstrated that IRS2 amplification was a recurrent event and that IRS2 levels modulated the sensibility of colorectal cancer cell lines to the dual IGF-1R/IR inhibitor BMS-754807. In addition, the authors, using public available SNP array data on tumors, observed that the frequency of IRS2 copy number gain (648 samples evaluated from four datasets) is higher in colorectal cancer compared to other tumor types (Huang, et al. 2015). |
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Entity | Pancreatic cancer |
Note | n the rat pancreas RINm5F cell line, Irs2, but not Irs1, phosphorylation was associated with IGF1 stimulated DNA synthesis (Zhang, et al. 1998). Kornmann and colleagues (Kornmann, et al. 1998) reported that IRS2 mRNA and protein were expressed in human pancreatic cancer cell lines (ASPC-1 and COLO-357), and highly expressed in primary pancreatic cancer samples compared with normal pancreatic samples. IGF1 and IGF2 enhanced cell growth, stimulated IRS2 tyrosine phosphorylation and IRS2/PI3K association in ASPC-1 and COLO-357 cells (Kornmann, et al. 1998). In AsPC-1 cell line, IGF1R/IRS2 axis controlled the VEGF transcription, indicating that this axis is an important mediator for tumor angiogenesis (Neid, et al. 2004). |
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Entity | Neuroblastoma |
Note | In SH-SY5Y, a human neuroblastoma cell line lacking IRS1, IGF1 stimulation leads to IGF1R activation and IRS2 phosphorylation, and activates PI3K and MAPK signaling (Kim, et al. 1998; Kim, et al. 2004). IRS2 also protects SH-EP and SH-SY5Y neuroblastoma cell lines from glucose-induced apoptosis by activation of PI3K/AKT and MAPK signaling (Kim, et al. 2009; Stohr, et al. 2011). |
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Entity | Hepatocellular carcinoma |
Note | Boissan and colleagues (Boissan, et al. 2005) reported an overexpression of IRS2 in murine models of hepatocarcinogenesis. IRS2 mRNA and protein were found to be overexpressed in human hepatoma cell lines and primary human hepatocellular carcinoma specimens (Boissan, et al. 2005; Cantarini, et al. 2006). Of note, inhibition of IRS2 by siRNA resulted in increased apoptosis in the hepatocellular carcinoma Hep3B cells. In the human hepatoma SMMC-7721 cell line, IRS2 silencing suppressed aflatoxin B1-induced PI3K/AKT and MAPK activation and cell migration (Ma, et al. 2012). Rashad and colleagues (Rashad, et al. 2014) observed, in 334 patients and 426 controls, that the D allele and the DD genotype of IRS2 G1057D (rs1805097) polymorphism were significantly associated with hepatocellular carcinoma risk. |
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Entity | Hematological malignancies |
Note | IRS2 expression was found to be downregulated in myelodysplastic syndrome patients compared with healthy donors (Machado-Neto, et al. 2012). Increased IRS2 expression and phosphorylation was observed during erythroid, granulocytic and megakaryocytic differentiation in establish leukemia cell line models (Machado-Neto, et al. 2012). IRS2 was found to be constitutively associated with JAK2 in the JAK2 V617F-mutated HEL cells, but not in the JAK2 wild type U937 cells (de Melo Campos, et al. 2016). In HEL cells, though not in U937 cells, IRS2 silencing reduced cell viability and increased apoptosis; these effects were enhanced when combined with ruxolitinib, a selective JAK1/2 inhibitor. In addition, CD34+ cells from JAK2V617F-mutated myeloproliferative neoplasm patients presented increased IRS2 mRNA levels (de Melo Campos, et al. 2016). Savage and colleagues (Savage, et al. 2015) described IRS2 mutations (S594W and H1328R) in three out of 22 chronic myeloid leukemia patients with tyrosine kinase inhibitors resistance. Expression of each of the two of the IRS2 mutations in Ba/F3 cells demonstrated transformation capacity in the absence of IL3 (Savage, et al. 2015). When co-expressed in Ba/F3 cells with BCR-ABL1, these IRS2 mutants conferred varying degrees of reduced sensitivity to imatinib in vitro (Savage, et al. 2015). |
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Entity | Glioblastoma |
Note | In a study focused on PI3K/AKT-related gene expression analysis in glioblastoma involving 103 patients, the IRS2 gene was amplified and overexpressed in 2 cases and IRS2 was also highly expressed in six cases with no demonstrated amplification (Knobbe, et al. 2003). Xu and colleagues (Xu, et al. 2011) identified IRS2 as a target of MicroRNA-153 and suggested that MicroRNA-153 suppressed PI3K/AKT signaling through IRS2 inhibition in the DBTRG-05MG human glioblastoma cell line. |
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Entity | Prostate cancer |
Note | Szabolcs and colleagues (Szabolcs, et al. 2009) reported a high expression of IRS2 in prostate cancer cell lines and in primary human prostate cancer samples, in which IRS2 was also correlated with MYC expression in prostate tumor samples. Ibuki et al. (Ibuki, et al. 2014) demonstrated an elevated IRS2 expression by immunohistochemistry in prostate cancer biopsies when compared to normal specimens. The in vitro treatment of LNCaP human prostate cancer cells with NT157, a IRS1/2 inhibitor, resulted in increased apoptosis and decreased cell proliferation (Ibuki, et al. 2014). Huang and colleagues (Huang, et al. 2012) observed that IRS2 rs7986346 polymorphism was associated with disease progression and impaired survival in prostate cancer patients treated with androgen-deprivation. |
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Entity | Thyroid cancer |
Note | In the FRTL-5 rat thyroid cell line, the "RET/PTC3 rearrangement" (inv(10)(q11q11) with NCOA4/ RET rearrangement), a constitutively activated tyrosine kinase receptor that is frequent in papillary thyroid cancer, induces IRS2 upregulation, and enhances IRS2/PI3K interaction and AKT activation (Miyagi, et al. 2004). Akker and colleagues (Akker, et al. 2014) observed no association between IRS2 G1057D (rs1805097) polymorphism and differentiated thyroid cancer development in a cohort of 93 differentiated thyroid cancer patients and 111 healthy controls. |
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Entity | Mesothelioma |
Note | IRS2 was found to be highly expressed in pleural mesothelioma samples and associated with cell motility in the H2461 cell line (Hoang, et al. 2004). |
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Entity | Clear cell renal cell carcinoma |
Note | Using semi-quantitative PCR, Al-Sarraf and colleagues (Al-Sarraf, et al. 2007) investigated IRS1, IRS2 and IRS5 mRNA expression in a cohort of 10 patients with clear cell renal carcinoma, comparing normal adjacent tissue with the respective tumor tissue for the analysis, and found an upregulation of IRS2 and IRS5 mRNA in tumor samples (Al-Sarraf, et al. 2007). |
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Entity | Endometrial cancer |
Note | Cayan and colleagues (Cayan, et al. 2010) reported that IRS2 G1057D (rs1805097) polymorphism was associated with the development of endometrial cancer in a cohort of 44 patients with colon cancer and 101 controls. |
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Entity | Malignant peripheral nerve sheath tumor |
Note | High expression of IRS2 was observed in malignant peripheral nerve sheath tumor compared to neurofibromas (Shaw, et al. 2012). IRS2 expression was also associated with reduced survival in malignant peripheral nerve sheath tumors using univariate analysis (Shaw, et al. 2012). |
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Entity | Bladder cancer |
Note | Using cDNA microarray analysis, Zekri and colleagues (Zekri, et al. 2015) found IRS2 upregulation among the genes differently expressed identified in bladder cancer. |
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Entity | Lung cancer |
Note | Park and colleagues (Park, et al. 2015) identified IRS2 as a MIR146A (MicroRNA-146a) target and suggested that MicroRNA-146a might suppress lung cancer progression by IRS2 inhibition. |
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Entity | Melanoma |
Note | In the MDA-MB-435 melanoma cell line, IRS2 signaling was identified as a key mediator of invasion promoted by α6β4 (Shaw 2001). In A375 human melanoma cells, the in vitro treatment with NT157, a IRS1/2 inhibitor, led to growth suppression of melanoma cells by degradation of IRS1 and IRS2 (Reuveni, et al. 2013). Moreover, NT157 strongly inhibited the development of lung metastases of melanoma cells in mouse models (Reuveni et al, 2013). |
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Entity | Esophageal squamous cell carcinoma |
Note | iu and colleagues (Liu, et al. 2015) identified IRS2 as a target of MicroRNA-146a and suggested that MicroRNA-146a suppressed esophageal squamous cell carcinoma growth through inhibition of IRS2. Corroborating these findings, in the MicroRNA-146a-expressing EC109 esophageal squamous cell carcinoma cell line, IRS2 recovery experiments increased cell growth. |
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Entity | Gastric cancer |
Note | Yamashita et al. (Yamashita, et al. 2006) described that IRS2 was methylation-silenced in gastric cancer specimens. Zhao and colleagues (Zhao, et al. 2012), reported that IRS2 G1057D (rs1805097) polymorphism was associated with increased susceptibility for gastric cancer in a cohort of 197 patients with gastric cancer and 156 age- and sex-matched controls. |
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Entity | Oral squamous cell carcinoma |
Note | Gao and colleagues (Gao, et al. 2014) described that IRS2 expression was negatively associated with histological differentiation of oral squamous cell carcinoma. In addition, IRS2 inhibition reduces cell proliferation, clonogenicity, cell cycle progression and PI3K/AKT activation in the human oral squamous cell carcinoma Tca-8113 cell line (Gao, et al. 2014). |
| |
Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer |
Akker M, Güldiken S, Sipahi T, Palabiyik O, Tosunolu A, elik Ö, Tunçbilek N, Sezer A, Süt N |
Mol Biol Rep 2014 May;41(5):3541-7 |
PMID 24504452 |
|
DOK4/IRS-5 expression is altered in clear cell renal cell carcinoma |
Al-Sarraf N, Reiff JN, Hinrichsen J, Mahmood S, Teh BT, McGovern E, De Meyts P, O'byrne KJ, Gray SG |
Int J Cancer 2007 Sep 1;121(5):992-8 |
PMID 17443497 |
|
Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling |
Argetsinger LS, Norstedt G, Billestrup N, White MF, Carter-Su C |
J Biol Chem 1996 Nov 15;271(46):29415-21 |
PMID 8910607 |
|
Overexpression of insulin receptor substrate-2 in human and murine hepatocellular carcinoma |
Boissan M, Beurel E, Wendum D, Rey C, Lécluse Y, Housset C, Lacombe ML, Desbois-Mouthon C |
Am J Pathol 2005 Sep;167(3):869-77 |
PMID 16127164 |
|
IRS-2 pathways integrate female reproduction and energy homeostasis |
Burks DJ, Font de Mora J, Schubert M, Withers DJ, Myers MG, Towery HH, Altamuro SL, Flint CL, White MF |
Nature 2000 Sep 21;407(6802):377-82 |
PMID 11014193 |
|
Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells |
Byron SA, Horwitz KB, Richer JK, Lange CA, Zhang X, Yee D |
Br J Cancer 2006 Nov 6;95(9):1220-8 |
PMID 17043687 |
|
Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms |
Cantarini MC, de la Monte SM, Pang M, Tong M, D'Errico A, Trevisani F, Wands JR |
Hepatology 2006 Aug;44(2):446-57 |
PMID 16871543 |
|
Interaction between leptin and insulin signaling pathways differentially affects JAK-STAT and PI 3-kinase-mediated signaling in rat liver |
Carvalheira JB, Ribeiro EB, Folli F, Velloso LA, Saad MJ |
Biol Chem 2003 Jan;384(1):151-9 |
PMID 12674509 |
|
Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer? Gynecol Endocrinol |
Cayan F, Tok E, Aras-Ates N, Ayaz L, Akbay E, Gen R, Karakas S, Dilek S |
2010 May;26(5):378-82 doi: 10 |
PMID 20184486 |
|
Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer |
Clark JL, Dresser K, Hsieh CC, Sabel M, Kleer CG, Khan A, Shaw LM |
Breast Cancer Res Treat 2011 Dec;130(3):759-72 |
PMID 21258861 |
|
Epidermal growth factor induces insulin receptor substrate-2 in breast cancer cells via c-Jun NH(2)-terminal kinase/activator protein-1 signaling to regulate cell migration |
Cui X, Kim HJ, Kuiatse I, Kim H, Brown PH, Lee AV |
Cancer Res 2006 May 15;66(10):5304-13 |
PMID 16707456 |
|
Progesterone crosstalks with insulin-like growth factor signaling in breast cancer cells via induction of insulin receptor substrate-2 |
Cui X, Lazard Z, Zhang P, Hopp TA, Lee AV |
Oncogene 2003 Oct 9;22(44):6937-41 |
PMID 14534541 |
|
IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer |
Day E, Poulogiannis G, McCaughan F, Mulholland S, Arends MJ, Ibrahim AE, Dear PH |
Int J Exp Pathol 2013 Jun;94(3):203-11 |
PMID 23594372 |
|
Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2 |
Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, Divisova J, Britton OL, Mohsin S, Allred DC, Hadsell DL, Lee AV |
Mol Cell Biol 2006 Dec;26(24):9302-14 |
PMID 17030631 |
|
Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II |
Feigelson HS, Teras LR, Diver WR, Tang W, Patel AV, Stevens VL, Calle EE, Thun MJ, Bouzyk M |
Breast Cancer Res 2008;10(4):R57 |
PMID 18611262 |
|
Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling |
Flashner-Abramson E, Klein S, Mullin G, Shoshan E, Song R, Shir A, Langut Y, Bar-Eli M, Reuveni H, Levitzki A |
Oncogene 2016 May 19;35(20):2675-80 |
PMID 26119932 |
|
Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels |
Folli F, Kahn CR, Hansen H, Bouchie JL, Feener EP |
A potential role for serine phosphorylation in insulin/angiotensin II crosstalk J Clin Invest |
PMID 9410892 |
|
IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma |
Gao L, Wang X, Wang X, Zhang L, Qiang C, Chang S, Ren W, Li S, Yang Y, Tong D, Chen C, Li Z, Song T, Zhi K, Huang C |
Oncotarget 2014 May 15;5(9):2562-74 |
PMID 24810113 |
|
Preclinical Effectiveness of Selective Inhibitor of IRS-1/2 NT157 in Osteosarcoma Cell Lines |
Garofalo C, Capristo M, Mancarella C, Reunevi H, Picci P, Scotlandi K |
Front Endocrinol (Lausanne) 2015 May 13;6:74 |
PMID 26029165 |
|
Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis |
Gibson SL, Ma Z, Shaw LM |
Cell Cycle 2007 Mar 15;6(6):631-7 |
PMID 17361103 |
|
Insulin resistance-related genes and advanced left-sided colorectal adenoma |
Gunter MJ, Hayes RB, Chatterjee N, Yeager M, Welch R, Schoen RE, Yakochi L, Schatzkin A, Peters U |
Cancer Epidemiol Biomarkers Prev 2007 Apr;16(4):703-8 |
PMID 17416760 |
|
Selective activation of insulin receptor substrate-1 and -2 in pleural mesothelioma cells: association with distinct malignant phenotypes |
Hoang CD, Zhang X, Scott PD, Guillaume TJ, Maddaus MA, Yee D, Kratzke RA |
Cancer Res 2004 Oct 15;64(20):7479-85 |
PMID 15492273 |
|
IRS2 copy number gain, KRAS and BRAF mutation status as predictive biomarkers for response to the IGF-1R/IR inhibitor BMS-754807 in colorectal cancer cell lines |
Huang F, Chang H, Greer A, Hillerman S, Reeves KA, Hurlburt W, Cogswell J, Patel D, Qi Z, Fairchild C, Ryseck RP, Wong TW, Finckenstein FG, Jackson J, Carboni JM |
Mol Cancer Ther 2015 Feb;14(2):620-30 |
PMID 25527633 |
|
Genetic variants in CASP3, BMP5, and IRS2 genes may influence survival in prostate cancer patients receiving androgen-deprivation therapy |
Huang SP, Bao BY, Hour TC, Huang CY, Yu CC, Liu CC, Lee YC, Huang CN, Pao JB, Huang CH |
PLoS One 2012;7(7):e41219 |
PMID 22844442 |
|
Progesterone receptor-B regulation of insulin-like growth factor-stimulated cell migration in breast cancer cells via insulin receptor substrate-2 |
Ibrahim YH, Byron SA, Cui X, Lee AV, Yee D |
Mol Cancer Res 2008 Sep;6(9):1491-8 |
PMID 18819936 |
|
The tyrphostin NT157 suppresses insulin receptor substrates and augments therapeutic response of prostate cancer |
Ibuki N, Ghaffari M, Reuveni H, Pandey M, Fazli L, Azuma H, Gleave ME, Levitzki A, Cox ME |
Mol Cancer Ther 2014 Dec;13(12):2827-39 |
PMID 25267499 |
|
Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines |
Jackson JG, Zhang X, Yoneda T, Yee D |
Oncogene 2001 Nov 1;20(50):7318-25 |
PMID 11704861 |
|
Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells |
Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, Pierce JH, O'Shea JJ |
Potential role of JAK kinases J Biol Chem |
PMID 7499365 |
|
Is there an association between variants in candidate insulin pathway genes IGF-I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population? Asian Pac J Cancer Prev |
Karimi K, Mahmoudi T, Karimi N, Dolatmoradi H, Arkani M, Farahani H, Vahedi M, Parsimehr E, Dabiri R, Nobakht H, Asadi A, Zali MR |
2013;14(9):5011-6 PubMed PMID: 24175768 |
PMID 24175768 |
|
Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis |
Kim B, Feldman EL |
Apoptosis 2009 May;14(5):665-73 |
PMID 19259821 |
|
Differential regulation of insulin receptor substrate-2 and mitogen-activated protein kinase tyrosine phosphorylation by phosphatidylinositol 3-kinase inhibitors in SH-SY5Y human neuroblastoma cells |
Kim B, Leventhal PS, White MF, Feldman EL |
Endocrinology 1998 Dec;139(12):4881-9 |
PMID 9832424 |
|
Insulin-like growth factor-I signaling in human neuroblastoma cells |
Kim B, van Golen CM, Feldman EL |
Oncogene 2004 Jan 8;23(1):130-41 |
PMID 14712218 |
|
Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3'-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas |
Knobbe CB, Reifenberger G |
Brain Pathol 2003 Oct;13(4):507-18 |
PMID 14655756 |
|
Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer |
Kornmann M, Maruyama H, Bergmann U, Tangvoranuntakul P, Beger HG, White MF, Korc M |
Cancer Res 1998 Oct 1;58(19):4250-4 |
PMID 9766646 |
|
The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2 |
Liu H, Ren G, Zhu L, Liu X, He X |
Tumour Biol 2016 Apr;37(4):4641-7 |
|
Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration |
Ma Y, Kong Q, Hua H, Luo T, Jiang Y |
PLoS One 2012;7(10):e47961 |
PMID 23112878 |
|
Downregulation of IRS2 in myelodysplastic syndrome: a possible role in impaired hematopoietic cell differentiation |
Machado-Neto JA, Favaro P, Lazarini M, da Silva Santos Duarte A, Archangelo LF, Lorand-Metze I, Costa FF, Saad ST, Traina F |
Leuk Res 2012 Jul;36(7):931-5 |
PMID 22465474 |
|
Hypoxia regulates insulin receptor substrate-2 expression to promote breast carcinoma cell survival and invasion |
Mardilovich K, Shaw LM |
Cancer Res 2009 Dec 1;69(23):8894-901 |
PMID 19920186 |
|
Chronic expression of RET/PTC 3 enhances basal and insulin-stimulated PI3 kinase/AKT signaling and increases IRS-2 expression in FRTL-5 thyroid cells |
Miyagi E, Braga-Basaria M, Hardy E, Vasko V, Burman KD, Jhiang S, Saji M, Ringel MD |
Mol Carcinog 2004 Oct;41(2):98-107 |
PMID 15378648 |
|
Estrogen receptor-alpha regulates the degradation of insulin receptor substrates 1 and 2 in breast cancer cells |
Morelli C, Garofalo C, Bartucci M, Surmacz E |
Oncogene 2003 Jun 26;22(26):4007-16 |
PMID 12821935 |
|
Involvement of insulin receptor substrate 2 in mammary tumor metastasis |
Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM |
Mol Cell Biol 2004 Nov;24(22):9726-35 |
PMID 15509777 |
|
Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells |
Neid M, Datta K, Stephan S, Khanna I, Pal S, Shaw L, White M, Mukhopadhyay D |
J Biol Chem 2004 Feb 6;279(6):3941-8 |
PMID 14604996 |
|
MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2 |
Park DH, Jeon HS, Lee SY, Choi YY, Lee HW, Yoon S, Lee JC, Yoon YS, Kim DS, Na MJ, Kwon SJ, Kim DS, Kang J, Park JY, Son JW |
Int J Oncol 2015 Oct;47(4):1545-53 |
PMID 26238771 |
|
4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice |
Patti ME, Sun XJ, Bruening JC, Araki E, Lipes MA, White MF, Kahn CR |
J Biol Chem 1995 Oct 20;270(42):24670-3 |
PMID 7559579 |
|
The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2 |
Platanias LC, Uddin S, Yetter A, Sun XJ, White MF |
J Biol Chem 1996 Jan 5;271(1):278-82 |
PMID 8550573 |
|
IRS1 is highly expressed in localized breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS2 is highly expressed in invasive breast tumors |
Porter HA, Perry A, Kingsley C, Tran NL, Keegan AD |
Cancer Lett 2013 Sep 28;338(2):239-48 |
PMID 23562473 |
|
Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma |
Rashad NM, El-Shal AS, Abd Elbary EH, Abo Warda MH, Hegazy O |
Cytokine 2014 Jul;68(1):50-8 |
PMID 24656929 |
|
Therapeutic destruction of insulin receptor substrates for cancer treatment |
Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R, Shir A, Herlyn M, Bar-Eli M, Levitzki A |
Cancer Res 2013 Jul 15;73(14):4383-94 |
PMID 23651636 |
|
Insulin induces tyrosine phosphorylation of JAK2 in insulin-sensitive tissues of the intact rat |
Saad MJ, Carvalho CR, Thirone AC, Velloso LA |
J Biol Chem 1996 Sep 6;271(36):22100-4 |
PMID 8703019 |
|
Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart |
Saad MJ, Velloso LA, Carvalho CR |
Biochem J 1995 Sep 15;310 ( Pt 3):741-4 |
PMID 7575404 |
|
Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling |
Sanchez-Lopez E, Flashner-Abramson E, Shalapour S, Zhong Z, Taniguchi K, Levitzki A, Karin M |
Oncogene 2016 May 19;35(20):2634-44 |
PMID 26364612 |
|
Association between IRS-2 G1057D polymorphism and risk of gastric cancer |
Zhao XM, Chen J, Yang L, Luo X, Xu LL, Liu DX, Zhai SL, Li P, Wang XR |
World J Gastrointest Oncol 2012 Jan 15;4(1):9-15 |
PMID 22347534 |
|
Activating Mutations of Insulin Receptor Substrate 2 (IRS2) in Patients with Tyrosine Kinase Inhibitor-Refractory Chronic Myeloid Leukemia.E |
Savage SL, Eide CA, Concannon KF, Bottomly D, Wilmot B, McWeeney SK, Maxson JE, Tyner JW, Tognon CE and Druker BJ. |
Blood (ASH Annual Meeting Abstracts) 2015 126 (23): Abstract #2461. |
|
Elevated expression of IRS2 in the progression from neurofibroma to malignant peripheral nerve sheath tumor |
Shaw CM, Grobmyer SR, Ucar DA, Cance WG, Reith JD, Hochwald SN |
Anticancer Res 2012 Feb;32(2):439-43 |
PMID 22287730 |
|
Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-OH kinase and promotion of invasion |
Shaw LM |
Mol Cell Biol 2001 Aug;21(15):5082-93 |
PMID 11438664 |
|
Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States |
Slattery ML, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, Byers T |
Breast Cancer Res Treat 2007 Aug;104(2):197-209 |
PMID 17051426 |
|
Insulin receptor substrate-1 and -2 mediate resistance to glucose-induced caspase-3 activation in human neuroblastoma cells |
Stöhr O, Hahn J, Moll L, Leeser U, Freude S, Bernard C, Schilbach K, Markl A, Udelhoven M, Krone W, Schubert M |
Biochim Biophys Acta 2011 May;1812(5):573-80 |
PMID 21354306 |
|
Role of IRS-2 in insulin and cytokine signalling |
Sun XJ, Wang LM, Zhang Y, Yenush L, Myers MG Jr, Glasheen E, Lane WS, Pierce JH, White MF |
Nature 1995 Sep 14;377(6545):173-7 |
PMID 7675087 |
|
Irs2 inactivation suppresses tumor progression in Pten+/- mice |
Szabolcs M, Keniry M, Simpson L, Reid LJ, Koujak S, Schiff SC, Davidian G, Licata S, Gruvberger-Saal S, Murty VV, Nandula S, Efstratiadis A, Kushner JA, White MF, Parsons R |
Am J Pathol 2009 Jan;174(1):276-86 |
PMID 19095950 |
|
Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3'-kinase |
Uddin S, Yenush L, Sun XJ, Sweet ME, White MF, Platanias LC |
J Biol Chem 1995 Jul 7;270(27):15938-41 |
PMID 7608146 |
|
Cross-talk between the insulin and angiotensin signaling systems |
Velloso LA, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR |
Proc Natl Acad Sci U S A 1996 Oct 29;93(22):12490-5 |
PMID 8901609 |
|
Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2 |
Verdier F, Chrétien S, Billat C, Gisselbrecht S, Lacombe C, Mayeux P |
An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation J Biol Chem |
PMID 9334184 |
|
The insulin signaling system |
White MF, Kahn CR |
J Biol Chem 1994 Jan 7;269(1):1-4 |
PMID 8276779 |
|
Disruption of IRS-2 causes type 2 diabetes in mice |
Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF |
Nature 1998 Feb 26;391(6670):900-4 |
PMID 9495343 |
|
Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells |
Wu S, Zhou B, Xu L, Sun H |
Oncol Rep 2010 Dec;24(6):1541-50 |
PMID 21042750 |
|
Chromatin-modifying drugs induce miRNA-153 expression to suppress Irs-2 in glioblastoma cell lines |
Xu J, Liao X, Lu N, Liu W, Wong CW |
Int J Cancer 2011 Nov 15;129(10):2527-31 |
PMID 21213215 |
|
Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray |
Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T |
Cancer Sci 2006 Jan;97(1):64-71 |
PMID 16367923 |
|
The IRS-signalling system during insulin and cytokine action |
Yenush L, White MF |
Bioessays 1997 Jun;19(6):491-500 |
PMID 9204766 |
|
IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer |
Yukseloglu EH, Celik SK, Kucuk MU, Yalin E, Ozkal SS, Ates C, Berkoz M, Yalin S, Ates NA |
Prz Gastroenterol 2014;9(2):88-92 |
PMID 25061488 |
|
Differentially expressed genes in metastatic advanced Egyptian bladder cancer |
Zekri AR, Hassan ZK, Bahnassy AA, Khaled HM, El-Rouby MN, Haggag RM, Abu-Taleb FM |
Asian Pac J Cancer Prev 2015;16(8):3543-9 |
PMID 25921176 |
|
Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line RINm5F is associated with phosphorylation of the insulin-like growth factor-I receptor and the insulin receptor substrate-2 |
Zhang Q, Berggren PO, Hansson A, Tally M |
J Endocrinol 1998 Mar;156(3):573-81 |
PMID 9582514 |
|
Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression |
Zhang X, Kamaraju S, Hakuno F, Kabuta T, Takahashi S, Sachdev D, Yee D |
Breast Cancer Res Treat 2004 Jan;83(2):161-70 |
PMID 14997047 |
|
Association between IRS-2 G1057D polymorphism and risk of gastric cancer |
Zhao XM, Chen J, Yang L, Luo X, Xu LL, Liu DX, Zhai SL, Li P, Wang XR |
World J Gastrointest Oncol 2012 Jan 15;4(1):9-15 |
PMID 22347534 |
|
IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in JAK2V617F-positive myeloproliferative neoplasms |
de Melo Campos P, Machado-Neto JA, Eide CA, Savage SL, Scopim-Ribeiro R, da Silva Souza Duarte A, Favaro P, Lorand-Metze I, Costa FF, Tognon CE, Druker BJ, Olalla Saad ST, Traina F |
Oncotarget 2016 Feb 9;7(6):6948-59 |
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