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IGF1R cancer

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https://www.readbyqxmd.com/read/29779108/microrna-dependent-regulation-of-igf1r-gene-expression-in-hormone-sensitive-and-hormone-resistant-prostate-cancer-cells
#1
V A Tarasov, M G Tyutyakina, M A Makhotkin, E F Shin, A V Naboka, A N Mashkarina, D A Chebotarev, E N Cherkasova, M I Kogan, M B Chibichyan, D G Matishov
Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells...
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#2
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731738/insulin-like-growth-factor-2-mrna-binding-protein-3-influences-sensitivity-to-anti-igf-system-agents-through-the-translational-regulation-of-igf1r
#3
Caterina Mancarella, Michela Pasello, Maria Cristina Manara, Lisa Toracchio, Evelina Fiorenza Sciandra, Piero Picci, Katia Scotlandi
Insulin-like growth factor 2 (IGF2) mRNA-binding protein 3 (IGF2BP3) is an oncofetal protein that binds RNA, thereby influencing the fate of target transcripts. IGF2BP3 is synthesized de novo in cancer, where it promotes proliferation, drug resistance, and metastasis via both IGF2-dependent and IGF2-independent mechanisms. Ewing sarcoma (ES) is a rare bone and soft tissue tumor in which the IGF system plays a pivotal role. This study aimed to investigate the effect of IGF2BP3 on the regulation of the IGF system in ES...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29725014/clinical-and-genomic-landscape-of-gastric-cancer-with-a-mesenchymal-phenotype
#4
Sang Cheul Oh, Bo Hwa Sohn, Jae-Ho Cheong, Sang-Bae Kim, Jae Eun Lee, Ki Cheong Park, Sang Ho Lee, Jong-Lyul Park, Yun-Yong Park, Hyun-Sung Lee, Hee-Jin Jang, Eun Sung Park, Sang-Cheol Kim, Jeonghoon Heo, In-Sun Chu, You-Jin Jang, Young-Jae Mok, WonKyung Jung, Baek-Hui Kim, Aeree Kim, Jae Yong Cho, Jae Yun Lim, Yuki Hayashi, Shumei Song, Elena Elimova, Jeannelyn S Estralla, Jeffrey H Lee, Manoop S Bhutani, Yiling Lu, Wenbin Liu, Jeeyun Lee, Won Ki Kang, Sung Kim, Sung Hoon Noh, Gordon B Mills, Seon-Young Kim, Jaffer A Ajani, Ju-Seog Lee
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy...
May 3, 2018: Nature Communications
https://www.readbyqxmd.com/read/29716918/igf2-ir-igf1r-pathway-in-tumor-cells-and-myofibroblasts-mediates-resistance-to-egfr-inhibition-in-cholangiocarcinoma
#5
Javier Vaquero, Cindy Lobe, Sylvana Tahraoui, Audrey Clapéron, Martine Mergey, Fatiha Merabtene, Dominique Wendum, Cédric Coulouarn, Chantal Housset, Christèle Desbois-Mouthon, Francoise Praz, Laura Fouassier
PURPOSE: Cholangiocarcinoma (CCA) is a desmoplastic tumor of the biliary tree in which epidermal growth factor receptor (EGFR) is overexpressed and contributes to cancer progression. Although, EGFR has been envisaged as a target for therapy, treatment with tyrosine kinase inhibitors (TKI) such as erlotinib did not provide therapeutic benefit in patients with CCA, emphasizing the need to investigate resistance mechanisms against EGFR inhibition. EXPERIMENTAL DESIGN: Resistant CCA cells to EGFR inhibition were obtained upon long time exposure of cells with erlotinib...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29709726/rna-sequencing-reveals-significant-mirnas-in-atypical-endometrial-hyperplasia
#6
Shiqian Tang, Yinmei Dai
PURPOSE: In this paper, we aimed to investigate the miRNAs that played a regulatory role in the development of atypical endometrial hyperplasia (AEH). METHODS: RNA sequencing was performed for endometrial tissues from 3 AEH patients and 3 endometrial normal hyperplasia patients. RNA sequencing data were processed and differentially expressed (DE) miRNAs were identified between AEH and controls. The target genes for DE miRNAs were identified and mapped to the protein-protein interaction (PPI) network...
March 19, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29693285/higher-variety-and-quantity-of-microrna-139-5p-isoforms-confer-suppressive-role-in-hepatocellular-carcinoma
#7
Hengli Ni, Xiaoxiao Dai, Xueqin Leng, Min Deng, Yan Qin, Qinghua Ji, Chunfang Xu, Jianming Li, Yao Liu
MiRNA isoforms (isomiRs) were defined as an addition or deletion of one or more nucleotides at the 5' or 3' ends or both. Different isomiRs of the same miRNA can target different genes, which have extended the regulatory scale medicated by miRNA. In this study, we systematically analyzed miRNA isoforms in hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas (TCGA) data and further explore their role by in silico and in vitro studies. We found that higher variety and quantity of miR-139-5p isoforms negatively correlated with the malignancy of HCC...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29669935/irs2-mutations-linked-to-invasion-in-pleomorphic-invasive-lobular-carcinoma
#8
Sha Zhu, B Marie Ward, Jun Yu, Asia N Matthew-Onabanjo, Jenny Janusis, Chung-Cheng Hsieh, Keith Tomaszewicz, Lloyd Hutchinson, Lihua Julie Zhu, Dina Kandil, Leslie M Shaw
Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29662006/hyperinsulinemia-promotes-esophageal-cancer-development-in-a-surgically-induced-duodeno-esophageal-reflux-murine-model
#9
Diletta Arcidiacono, Arben Dedja, Cinzia Giacometti, Matteo Fassan, Daniele Nucci, Simona Francia, Federico Fabris, Alice Zaramella, Emily J Gallagher, Mauro Cassaro, Massimo Rugge, Derek LeRoith, Alfredo Alberti, Stefano Realdon
Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29644076/lost-in-translation-the-3-utr-of-igf1r-as-an-ancient-long-noncoding-rna
#10
Avantika Mainieri, David Haig
Background and objectives: The insulin-like growth factor (IGF) signaling system is a major arena of intragenomic conflict over embryonic growth between imprinted genes of maternal and paternal origin and the IGF type 1 receptor (IGF1R) promotes proliferation of many human cancers. The 3'-untranslated region (3'-UTR) of the mouse Igf1r mRNA is targeted by miR-675-3p derived from the imprinted H19 long noncoding RNA. We undertook a comparative sequence analysis of vertebrate IGF1R 3'-UTRs to determine the evolutionary history of miR-675 target sequences and to identify conserved features that are likely to be involved in post-transcriptional regulation of IGF1R translation...
2018: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/29642855/mir-30a-5p-confers-cisplatin-resistance-by-regulating-igf1r-expression-in-melanoma-cells
#11
Yuxia Li, Jie Zhang, Yajing Liu, Bingyue Zhang, Fubo Zhong, Shubin Wang, Zhengyu Fang
BACKGROUND: Melanoma is notoriously resistant to all current modalities of cancer therapies including chemotherapy. In recent years, microRNAs (miRNAs) have emerged as molecular regulators in the development and progression of melanoma. However, the relationship between microRNA and chemo-resistance of melanoma is little known. In present study, we aimed to investigate the miRNAs related to cisplatin-resistance in melanoma cells. METHODS: After cisplatin (DDP) resistant melanoma cells (M8/DDP and SK-Mel-19/DDP) were established in-vitro, high-throughput screening of differentially expressed miRNAs between resistant cells and parental cells were performed...
April 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29621572/identification-of-a-unique-loss-of-function-mutation-in-igf1r-and-a-crosstalk-between-igf1r-and-wnt-%C3%AE-catenin-signaling-pathways
#12
Gayatri Jamwal, Gurjinder Singh, Mohd Saleem Dar, Paramjeet Singh, Nasima Bano, Sajad Hussain Syed, Padmani Sandhu, Yusuf Akhter, Satdarshan P Monga, Mohd Jamal Dar
IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. Overexpression of the IGF1R in these malignancies is associated with a poor prognosis and overall survival. IGF1R specific kinase inhibitors have failed in multiple clinical trials partly because of the complex nature of IGF1R signaling. Thus identifying new binding partners and allosteric sites on IGF1R are emerging areas of research...
April 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29620219/anthricin%C3%A2-induced-caspase%C3%A2-dependent-apoptosis-through-igf1r-pi3k-akt-pathway-inhibition-in-a549-human-non%C3%A2-small-lung-cancer-cells
#13
Bo-Ram Park, Seul Ah Lee, Sung Min Moon, Chun Sung Kim
Anthricin (deoxypodophyllotoxin) is a major lignan in Anthriscus sylvestris and possesses many bioactivities such as antiproliferative, antitumor, anti‑platelet aggregation, antiviral and anti‑inflammatory actions. However, the anticancer effects of anthricin on A549 human non‑small cell lung cancer cells and potential molecular mechanisms remain unknown. Therefore, we investigated the anticancer effect of anthricin and the underlying mechanism in A549 cells. Anthricin (10‑200 nM) inhibited the viability of A549 cells in a dose‑ and time‑dependent manner...
March 27, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29615978/genome-wide-analyses-identify-filamin-a-as-a-novel-downstream-target-for-insulin-and-igf1-action
#14
Daniel Aizen, Metsada Pasmanik-Chor, Rive Sarfstein, Zvi Laron, Ilan Bruchim, Haim Werner
Insulin analogs were developed to improve diabetes therapy. However, certain modifications introduced into the insulin molecule were shown to enhance their affinity to the insulin-like growth factor-1 receptor (IGF1R). Most tumors, including endometrial cancers, express high levels of IGF1R. The present study was aimed at identifying the entire set of genes that are differentially activated by insulin glargine or detemir, in comparison to insulin and IGF1, in Type 1 and Type 2 endometrial cancer cell lines (ECC-1 and USPC-1, respectively)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29610318/ablation-of-insulin-receptor-substrates-1-and-2-suppresses-kras-driven-lung-tumorigenesis
#15
He Xu, Min-Sik Lee, Pei-Yun Tsai, Ashley S Adler, Natasha L Curry, Saketh Challa, Elizaveta Freinkman, Daniel S Hitchcock, Kyle D Copps, Morris F White, Roderick T Bronson, Michael Marcotrigiano, Yaotang Wu, Clary B Clish, Nada Y Kalaany
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma ( KRAS ). Although KRAS direct binding to and activation of PI3K is required for KRAS -driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 ( Irs1 / Irs2 ), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29599290/tgf%C3%AE-and-igf1r-signaling-activate-protein-kinase-a-through-differential-regulation-of-ezrin-phosphorylation-in-colon-cancer-cells
#16
Premila D Leiphrakpam, Michael G Brattain, Jennifer D Black, Jenny Jing Wang
Aberrant cell survival plays a critical role in cancer progression and metastasis. We have previously shown that ezrin, a cAMP-dependent A-kinase anchoring protein (AKAP), is upregulated in colorectal cancer (CRC) liver metastasis. Phosphorylation of ezrin at threonine 567(T567) activates ezrin and plays an important role in CRC cell survival associated with XIAP and survivin upregulation. In this study, we demonstrate that, in FET and GEO colon cancer cells, knockdown of ezrin expression or inhibition of ezrin phosphorylation at T567 increases apoptosis through PKA activation in a cAMP-independent manner...
March 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29574877/fisetin-mediated-apoptotic-cell-death-in-parental-and-oxaliplatin-irinotecan-resistant-colorectal-cancer-cells-in-vitro-and-in-vivo
#17
Long-Bin Jeng, Bharath Kumar Velmurugan, Ming-Cheng Chen, Hsi-Hsien Hsu, Tsung-Jung Ho, Cecilia-Hsuan Day, Yueh-Min Lin, V Vijaya Padma, Chuan-Chou Tu, Chih-Yang Huang
Irinotecan (CPT11) and Oxaliplatin have been used in combination with fluorouracil and leucovorin for treating colorectal cancer. However, the efficacy of these drugs is reduced due to various side effects and drug resistance. Fisetin, a hydroxyflavone possess anti-proliferative, anti-cancer, anti-inflammatory, and antioxidant activity against various types of cancers. Apart from that, fisetin has been shown to induce cytotoxic effects when combined with other known chemotherapeutic drugs. In this study, we aimed to investigate whether Fisetin was capable of sensitizing both Irinotecan and Oxaliplatin resistance colon cancer cells and explored the possible signaling pathways involved using In vitro and In vivo models...
March 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29559623/suppressor-of-cytokine-signalling-2-limits-igf1r-mediated-regulation-of-epithelial-mesenchymal-transition-in-lung-adenocarcinoma
#18
Yue Zhou, Zhilei Zhang, Ning Wang, Jizheng Chen, Xu Zhang, Min Guo, Li John Zhong, Qian Wang
Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma, is the leading cause of death from lung malignancies and has a poor prognosis due to metastasis. Suppressor of cytokine signalling-2 (SOCS2), a feedback inhibitor of cytokine signalling, has been shown to be involved in growth control. Here, we show that SOCS2 were significantly downregulated in tumour foci in NSCLC patients. The expression levels of SOCS2 significantly correlated with clinical stage, lymph node metastasis, histological subtype and survival time...
March 20, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29549306/circhipk3-promotes-colorectal-cancer-growth-and-metastasis-by-sponging-mir-7
#19
Kaixuan Zeng, Xiaoxiang Chen, Mu Xu, Xiangxiang Liu, Xiuxiu Hu, Tao Xu, Huiling Sun, Yuqin Pan, Bangshun He, Shukui Wang
Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2...
March 16, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29486734/the-association-of-diabetes-mellitus-and-insulin-treatment-with-expression-of-insulin-related-proteins-in-breast-tumors
#20
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
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