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IGF-1R phosphorylation

Wei Ma, Weiye Feng, Jie Tan, Airu Xu, Yudong Hu, Lanlan Ning, Yanhong Kang, Liuqian Wang, Ziwen Zhao
Background: Recently, studies have demonstrated that microRNA-497 (miR-497) plays an important role 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) in treatment of non-small cell lung cancer (NSCLC) is not fully understood. In this study, we explored the potential of miR-497 in targeting the insulin-like growth factor-1 receptor (IGF-1R) signaling pathways to overcome gefitinib resistance...
October 2018: Journal of Thoracic Disease
Baohui Qi, Ying Yang, Guowei Gong, Huan He, Xupeng Yue, Xin Xu, Yun Hu, Junming Li, Tao Chen, Xiaobing Wan, Anmian Zhang, Guobiao Zhou
A series of 21 novel N1 -(2-aryl-1,3-thiazolidin-4-one)-N3 -aryl urea derivatives based on the previously identified lead compound I were synthesized and biologically characterized. The most promising compound 19a was identified as a multi-tyrosine kinase inhibitor, including c-Met, Ron, c-Kit, AXL and IGF-1R, etc. The results of real-time live-cell imaging indicated that compound 19a showed improved cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, with an efficacy that was significantly greater than Cabozantinib...
November 23, 2018: European Journal of Medicinal Chemistry
Changhui Li, Shouyun Zhang, Tongguo Qiu, Yuanji Wang, David M Ricketts, Chao Qi
OBJECTIVE: To investigate the role and mechanism of action of nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in osteosarcoma (OS). METHODS: Bioinformatic analysis suggested miR-320a as potential target of NNT-AS1. Influence of NNT-AS1 overexpression or knockdown on OS cell proliferation, colony-formation, apoptosis, migration and invasion capacity was first investigated. Expression levels of NNT-AS1, miR-320a, beta-catenin, RUNX2, IGF-1R, c-Myc, Cyclin D1 and MMP13 were also evaluated by RT-qPCR and western blotting accordingly...
November 29, 2018: Cancer Biology & Therapy
Xia Chen, Ruhong Zhang, Qun Zhang, Zhicheng Xu, Feng Xu, Datao Li, Yiyuan Li
OBJECTIVE: To explore the effectiveness of the insulin-like growth factor 1 receptor (IGF-1R)/PI3K/AKT pathway in promoting the synthesis of the auricular chondrocyte extracellular matrix (ECM) using concentrated growth factor (CGF). METHODS: Chondrocytes isolated from the remnant auricular cartilage of microtia patients were randomly divided into different experimental and control groups, then stimulated with a reagent. IGF-1 released by CGF was quantified by enzyme-linked immunosorbent assay...
November 23, 2018: Journal of Cellular Physiology
Vanessa Delcroix, Olivier Mauduit, Nolwenn Tessier, Anaïs Montillaud, Tom Lesluyes, Thomas Ducret, Frédéric Chibon, Fabien Van Coppenolle, Sylvie Ducreux, Pierre Vacher
By inhibiting Insulin-Like Growth Factor-1-Receptor (IGF-1R) signaling, Klotho (KL) acts like an aging- and tumor-suppressor. We investigated whether KL impacts the aggressiveness of liposarcomas, in which IGF-1R signaling is frequently upregulated. Indeed, we observed that a higher KL expression in liposarcomas is associated with a better outcome for patients. Moreover, KL is downregulated in dedifferentiated liposarcomas (DDLPS) compared to well-differentiated tumors and adipose tissue. Because DDLPS are high-grade tumors associated with poor prognosis, we examined the potential of KL as a tool for overcoming therapy resistance...
November 14, 2018: Cancers
Jiao Luo, Nyam-Osor Chimge, Beiyun Zhou, Per Flodby, Alessandra Castaldi, Amy L Firth, Yixin Liu, Hongjun Wang, Chenchen Yang, Crystal N Marconett, Edward D Crandall, Ite A Offringa, Baruch Frenkel, Zea Borok
Claudins are a family of transmembrane proteins integral to the structure and function of tight junctions (TJ). Disruption of TJ and alterations in claudin expression are important features of invasive and metastatic cancer cells. Expression of CLDN18.1, the lung-specific isoform of CLDN18, is markedly decreased in lung adenocarcinoma (LuAd). Furthermore, we recently observed that aged Cldn18 -/- mice have increased propensity to develop LuAd. We now demonstrate that CLDN18.1 expression correlates inversely with promoter methylation and with LuAd patient mortality...
December 15, 2018: International Journal of Cancer. Journal International du Cancer
Liang Li, Shuchen Liu, Liyuan Liu, Zhongbing Ma, Man Feng, Chunmiao Ye, Wenzhong Zhou, Yongjiu Wang, Lu Liu, Fei Wang, Lixiang Yu, Fei Zhou, Yujuan Xiang, Shuya Huang, Qinye Fu, Qiang Zhang, Dezong Gao, Zhigang Yu
The expression of insulin-like growth factor-1 receptor (IGF-1R), which is involved in the genesis and progression of breast cancer, is thought to be associated with the overall survival (OS) of patients. However, the predictive and prognostic significance of the IGF-1R expression in breast cancer remains controversial. The present study aimed to identify the factors associated with the levels of phosphorylated (p)-IGF-1R in breast cancer, their impact on the outcomes of breast cancer patients, and the prognostic value of alterations of p-IGF-1R during neoadjuvant chemotherapy (NAC)...
October 2018: Experimental and Therapeutic Medicine
Hua Wang, Hao Zhang, Fuming Cao, Jiaping Lu, Jin Tang, Huizhi Li, Yiyun Zhang, Bo Feng, Zhaosheng Tang
The present study investigated whether insulin‑like growth factor‑1 (IGF‑1) exerts a protective effect against neuropathy in diabetic mice and its potential underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db (diabetes), IGF‑1‑treated db/db and IGF‑1‑picropodophyllin (PPP)‑treated db/db. Behavioral studies were conducted using the hot plate and von Frey methods at 6 weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the sciatic nerve was measured using a neurophysiological method at 8 weeks of age...
September 3, 2018: Molecular Medicine Reports
Haitao Wang, Xiaoying Su, Jiankang Fang, Xingan Xin, Xia Zhao, Uma Gaur, Qiang Wen, Jiangping Xu, Peter J Little, Wenhua Zheng
The insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) facilitate tumor proliferation and progression. Tanshinone IIA (TSN) is an active diterpene quinone isolated from the roots of the herbal plant Salvia miltiorrhiza . TSN inhibits the proliferation of various types of cancer cells but its role in the IGF-1R-induced proliferation of pheochromocytoma (PC12) cells and the potential mechanisms are largely unknown. This study aims to investigate the anti-proliferative effect of TSN in PC12 cells and its role on IGF-1R signaling transduction...
September 12, 2018: International Journal of Molecular Sciences
Parag P Patwardhan, Elgilda Musi, Gary K Schwartz
Sarcomas are rare cancers that make up about 1% of all cancers in adults; however, they occur more commonly among children and young adolescents. Sarcomas are genetically complex and are often difficult to treat given the lack of clinical efficacy of any of the currently available therapies. Receptor tyrosine kinases (RTK) such as c-Kit, c-Met, PDGFR, IGF-1R, as well as FGFR have all been reported to be involved in driving tumor development and progression in adult and pediatric soft-tissue sarcoma. These driver kinases often act as critical determinants of tumor cell proliferation and targeting these signal transduction pathways remains an attractive therapeutic approach...
November 2018: Molecular Cancer Therapeutics
Jingtao Zhang, Guilan Wen, Longhua Sun, Wenxin Yuan, Ran Wang, Qinghua Zeng, Guangyi Zhang, Bentong Yu
Lung cancer is one of the most commonly diagnosed malignancies worldwide. Cryptotanshinone (CPT) is a diterpene quinone compound extracted from natural plants and has been reported to have anticancer effects in several cancers including human lung cancer. However, the mechanism by which CPT acts to prevent lung cancer cell growth is largely unknown. In the present study, by using MTT assay, colony formation assay, wound healing and western blotting assays, the effects of CPT on the cell proliferation and migration of human lung cancer cells and the potential cellular signaling mechanisms were investigated...
November 2018: Oncology Reports
Kewei Ren, Jilei Tang, Xuefeng Jiang, Huiqing Sun, Luming Nong, Nan Shen, Yanqing Gu
BACKGROUND/AIMS: The biological effects of periodic mechanical stress on the mitogenesis of chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying the ability of chondrocytes to sense and respond to mechanical stimuli remain to be determined. In the current study, we analyzed the mechanisms by which periodic mechanical stress is translated into biochemical signals and verified the key role of non-integrin mechanosensors including Caveolin-1 (Cav-1), and insulin-like growth factor-1 receptor (IGF-1R) in chondrocyte proliferation...
2018: Cellular Physiology and Biochemistry
Daniel J Heidenberg, Nora M Haney, Bashir M Rezk, Sudha Talwar, Samuel C Okpechi, Sudesh K Srivastav, Matthew Honda, Bryant Song, Kevin Swan, Salah Awadallah, James Anaissie, Taylor Peak, Kenneth J DeLay, Phillip J Kadowitz, Suresh C Sikka, Asim B Abdel Mageed, Wayne J G Hellstrom
To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n  = 7). The third group received BCNI and Pio treatment (BCNI  +  Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI  +  Pio  +  JB-1, n = 7)...
August 2, 2018: International Journal of Impotence Research
Liang Hu, Fei Han, Lin Chen, Xie Peng, Daiwen Chen, De Wu, Lianqiang Che, Keying Zhang
Background: Intrauterine growth-restricted (IUGR) neonates impair postnatal skeletal muscle growth. The aim of this study was to investigate whether high nutrient intake (HNI) during the suckling period could improve muscle growth and metabolic status of IUGR pigs. Methods: Twelve pairs of IUGR and normal birth weight (NBW) pigs (7 days old) were randomly assigned to adequate nutrient intake and HNI formula milk groups. Psoas major (PM) muscle sample was obtained after 21 days of rearing...
2018: Genes & Nutrition
Yih Ho, Yu-Chen Sh Yang, Yu-Tang Chin, Szu-Yi Chou, Yi-Ru Chen, Ya-Jung Shih, Jacqueline Whang-Peng, Chun A Changou, Hsuan-Liang Liu, Shwu-Jiuan Lin, Heng-Yuan Tang, Hung-Yun Lin, Paul J Davis
Leiomyomas (myomas) are the most common benign smooth muscle cell tumor of the myometrium. Resveratrol, a stilbene, has been used as an anti-inflammatory and antitumor agent. In the current study, we investigated the inhibitory effect of resveratrol on the proliferation of primary human myoma cell cultures. Resveratrol arrested cell proliferation via integrin αvβ3. It also inhibited integrin αvβ3 expression and protein accumulation. Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol...
October 2018: Food and Chemical Toxicology
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mu, Gang Yang
Pituitary corticotroph tumors lead to excess adrenocorticotrophic hormone (ACTH) secretion, resulting in Cushing's disease (CD), which is associated with significant mortality. Standard treatments include neurosurgery, radiotherapy and medical therapy. Both surgery and radiotherapy have undesirable complications and high recurrence rates. At present, there is only one medical option available that targets pituitary adenoma and ACTH secretion, the drug pasireotide. However, hyperglycemia is common during pasireotide treatment...
July 17, 2018: Molecular and Cellular Endocrinology
Bin Yan, Minjun Huang, Canjun Zeng, Na Yao, Jie Zhang, Bo Yan, Huaji Jiang, Xinggui Tian, Xiang Ao, Huiyu Zhao, Wen Zhou, Jun Chu, Liping Wang, Cory J Xian, Zhongmin Zhang, Liang Wang
BACKGROUND/AIMS: Narrowing of the lumbar spinal canal is a condition called lumbar spinal stenosis (LSS) and is a high-morbidity problem in the elderly. LSS is commonly caused by hypertrophy of the ligamentum flavum (HLF). Previous studies showed that fibrosis of the ligamentum flavum (LF) largely contributed to HLF. However, the underlying pathomechanism remains unclear. Insulin-like growth factor-1 (IGF-1) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding IGF-1 in HLF...
2018: Cellular Physiology and Biochemistry
Yong-Jian Hu, Qian Sun, Wen-Hua Zhang, Yu-Jia Huo, Chan-Juan Xu, Jian-Feng Liu
Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-II metabotropic glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor. The group-II mGlu receptors are promising antipsychotic targets, but the specific role of mGlu2 signaling remains unclear. Receptor tyrosine kinases (RTKs) are also believed to participate in brain pathogenesis. To investigate whether there is any communication between mGlu2 and RTKs, we generated a CHO-mGlu2 cell line that stably expresses mGlu2 and showed that activation of mGlu2 by LY379268, a group II mGlu agonist, was able to transactivate insulin-like growth factor 1 receptor (IGF-1R)...
June 26, 2018: Acta Pharmacologica Sinica
Olalekan M Ogundele, Joaquin Pardo, Joseph Francis, Rodolfo G Goya, Charles C Lee
Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways. These proteins (CaMKIIα and MAPK) regulate Ca2+ movement and long-term potentiation (LTP)...
2018: Frontiers in Neuroanatomy
Na Liu, Hua Yang, Hong Wang
Background: In recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC. Materials and methods: We analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients...
2018: OncoTargets and Therapy
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