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IGF1R cancer

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https://www.readbyqxmd.com/read/28075048/the-sti-and-uba-domains-of-ubqln1-are-critical-determinants-of-substrate-interaction-and-proteostasis
#1
Zimple Kurlawala, Parag P Shah, Charmi Shah, Levi J Beverly
There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders ranging from Alzheimer's disease to cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28067383/the-functional-consequences-and-prognostic-value-of-dosage-sensitivity-in-ovarian-cancer
#2
Zichuang Yan, Yongjing Liu, Yunzhen Wei, Ning Zhao, Qiang Zhang, Cheng Wu, Zhiqiang Chang, Yan Xu
Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression...
January 9, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28064447/up-regulation-of-mir-497-confers-resistance-to-temozolomide-in-human-glioma-cells-by-targeting-mtor-bcl-2
#3
Danhua Zhu, Ming Tu, Bo Zeng, Lin Cai, Weiming Zheng, Zhipeng Su, Zhengquan Yu
The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR-497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR-497 was markedly up-regulated in TMZ-resistant glioma cells; high miR-497 expression level was associated with TMZ-resistant phenotype of glioma cells...
January 8, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28062706/combinatorial-drug-screening-identifies-ewing-sarcoma-specific-sensitivities
#4
Branka Radic-Sarikas, Kalliopi P Tsafou, Kristina B Emdal, Theodore Papamarkou, Kilian V M Huber, Cornelia Mutz, Jeffrey A Toretsky, Keiryn L Bennett, Jesper V Olsen, Søren Brunak, Heinrich Kovar, Giulio Superti-Furga
Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28043364/inhibition-of-peripubertal-sheep-mammary-gland-development-by-cysteamine-through-reducing-progesterone-and-growth-factor-production
#5
Yong Zhao, Yanni Feng, Hongfu Zhang, Xin Kou, Lan Li, Xinqi Liu, Pengfei Zhang, Liantao Cui, Meiqiang Chu, Wei Shen, Lingjiang Min
Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets...
February 2017: Theriogenology
https://www.readbyqxmd.com/read/28032929/downregulation-of-mir-100-mir-125b-is-associated-with-lymph-node-metastasis-in-early-colorectal-cancer-with-submucosal-invasion
#6
Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation despite very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28030849/combined-and-individual-tumor-specific-expression-of-insulin-like-growth-factor-i-receptor-insulin-receptor-and-phospho-insulin-like-growth-factor-i-receptor-insulin-receptor-in-primary-breast-cancer-implications-for-prognosis-in-different-treatment-groups
#7
Sofie Björner, Ann H Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström
Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection.Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a population-based cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017727/silencing-hs6st3-inhibits-growth-and-progression-of-breast-cancer-cells-through-suppressing-igf1r-and-inducing-xaf1
#8
Omid Iravani, Boon-Huat Bay, George Wai-Cheong Yip
Heparan sulfate 6-O-sulfation is biologically edited by 6-O-sulfotransferases (HS6STs) within heparan sulfate chains. Three isoforms of HS6ST have been identified. These enzymes are found to be differentially expressed in a variety of tissues. Recently, several studies have shown that dysregulation of 6-O-sulfotransferases could be involved in tumorigenesis of several cancers. This study aimed to analyze the expression and function of HS6ST3 in breast cancer. HS6ST3 was found up-regulated in T47D, MCF7 and MDA-MB231 breast cancer cell lines...
December 23, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27989801/molecular-checkpoint-decisions-made-by-subverted-vascular-niche-transform-indolent-tumor-cells-into-chemoresistant-cancer-stem-cells
#9
Zhongwei Cao, Joseph M Scandura, Giorgio G Inghirami, Koji Shido, Bi-Sen Ding, Shahin Rafii
Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R)...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27964748/non-coding-single-nucleotide-variants-affecting-estrogen-receptor-binding-and-activity
#10
Amir Bahreini, Kevin Levine, Lucas Santana-Santos, Panayiotis V Benos, Peilu Wang, Courtney Andersen, Steffi Oesterreich, Adrian V Lee
BACKGROUND: Estrogen receptor (ER) activity is critical for the development and progression of the majority of breast cancers. It is known that ER is differentially bound to DNA leading to transcriptomic and phenotypic changes in different breast cancer models. We investigated whether single nucleotide variants (SNVs) in ER binding sites (regSNVs) contribute to ER action through changes in the ER cistrome, thereby affecting disease progression. Here we developed a computational pipeline to identify SNVs in ER binding sites using chromatin immunoprecipitation sequencing (ChIP-seq) data from ER+ breast cancer models...
December 13, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27956702/snail-modulated-mir-493-forms-a-negative-feedback-loop-with-igf1r-pathway-and-blocks-tumorigenesis
#11
Arathy S Kumar, Sankar Jagadeeshan, Ravi Shankar Pitani, Vijayalakshmi Ravishankar, Kesavan Venkitasamy, Ganesh Venkatraman, Suresh K Rayala
In this study, we have identified one microRNA - miR-493, which could simultaneously and directly regulate multiple genes downstream of IGF1R pathway including IGF1R, by binding with complementary sequences in the 3' UTR of mRNAs of IGF1R, IRS1 and MAPK1, thereby potentiating their inhibitory function at multiple levels in development and progression of cancers. This binding was further confirmed by pull down of miR with AGO-2 antibody. Further, results from head and neck samples showed that miR-493 levels were significantly downregulated in tumors with a concomitant increase in the expression of IGF1R and key downstream effectors...
December 12, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27891760/muscle-ras-oncogene-homolog-mras-recurrent-mutation-in-borrmann-type-iv-gastric-cancer
#12
Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27879396/integrating-network-reconstruction-with-mechanistic-modeling-to-predict-cancer-therapies
#13
Melinda Halasz, Boris N Kholodenko, Walter Kolch, Tapesh Santra
Signal transduction networks are often rewired in cancer cells. Identifying these alterations will enable more effective cancer treatment. We developed a computational framework that can identify, reconstruct, and mechanistically model these rewired networks from noisy and incomplete perturbation response data and then predict potential targets for intervention. As a proof of principle, we analyzed a perturbation data set targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) pathways in a panel of colorectal cancer cells...
November 22, 2016: Science Signaling
https://www.readbyqxmd.com/read/27862334/tgf%C3%AE-signaling-confers-sorafenib-resistance-via-induction-of-multiple-rtks-in-hepatocellular-carcinoma-cells
#14
Nathan Ungerleider, Chang Han, Jinqiang Zhang, Lu Yao, Tong Wu
Transforming growth factor β (TGFβ) is a multifunctional cytokine which is importantly implicated in hepatocarcinogenesis. The current study provides novel evidence that TGFβ upregulates the expression of multiple receptor tyrosine kinases (RTKs), including IGF1R, EGFR, PDGFβR, and FGFR1 in human hepatocellular carcinoma (HCC) cells. This, in turn, sensitized HCC cells to individual cognate RTK ligands, leading to cell survival. Our data showed that the TGFβ-mediated increase in growth factor sensitivity led to evasion of apoptosis induced by the mutikinase inhibitor, sorafenib...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27861515/involvement-of-igf1r-in-bronchiolar-epithelial-regeneration-role-during-repair-kinetics-after-selective-club-cell-ablation
#15
Icíar P López, Sergio Piñeiro-Hermida, Rosete S Pais, Raquel Torrens, Andreas Hoeflich, José G Pichel
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny...
2016: PloS One
https://www.readbyqxmd.com/read/27858328/adverse-events-and-efficacy-of-cixutumumab-in-phase-ii-clinical-trials-a-systematic-review-and-meta-analysis
#16
REVIEW
Hongxin Cao, Lixuan Cui, Wei Ma, Linhai Zhu, Kai Wang, Yang Ni, Yibing Wang, Jiajun Du
BACKGROUND AND OBJECTIVES: Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials. METHODS: Data were collected from PubMed, Embase, and Clinicaltrials.gov. The improvement on progression-free survival (PFS) was evaluated by hazard ratio (HR) and 95% confidence intervals (95% CIs)...
November 17, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-phosphatidylinositol-3-kinase-pi3k-akt-pathway
#17
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
G protein-coupled receptors (GPCRs) activate PI3K/v-AKT thymoma viral oncoprotein (AKT) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH via PKA activates the PI3K/AKT cascade. Insulin-like growth factor 1 (IGF1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1 receptor (IGF1R) but, in the absence of FSH, fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27836546/apbb1-reinforces-cancer-stem-cell-and-epithelial-to-mesenchymal-transition-by-regulating-the-igf1r-signaling-pathway-in-non-small-cell-lung-cancer-cells
#18
Jei Ha Lee, Jung Yul Kim, Seo Yeon Kim, Soo Im Choi, Kuk Chan Kim, Eun Wie Cho, In Gyu Kim
Amyloid β precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells...
January 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27813496/the-cea-lo-colorectal-cancer-cell-population-harbors-cancer-stem-cells-and-metastatic-cells
#19
Chang Yan, Yibing Hu, Bo Zhang, Lei Mu, Kaiyu Huang, Hui Zhao, Chensen Ma, Xiaolan Li, Deding Tao, Jianping Gong, Jichao Qin
Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27808166/lpa-receptor-activity-is-basal-specific-and-coincident-with-early-pregnancy-and-involution-during-mammary-gland-postnatal-development
#20
Deanna Acosta, Susmita Bagchi, Pilib Ó Broin, Daniel Hollern, Silvia E Racedo, Bernice Morrow, Rani S Sellers, John M Greally, Aaron Golden, Eran Andrechek, Teresa Wood, Cristina Montagna
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages...
November 3, 2016: Scientific Reports
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