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FGF Receptor

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https://www.readbyqxmd.com/read/29030113/proteomic-analyses-of-signalling-complexes-associated-with-receptor-tyrosine-kinase-identify-novel-members-of-fibroblast-growth-factor-receptor-3-interactome
#1
Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3)...
October 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29017058/androgen-receptor-pathway-independent-prostate-cancer-is-sustained-through-fgf-signaling
#2
Eric G Bluemn, Ilsa M Coleman, Jared M Lucas, Roger T Coleman, Susana Hernandez-Lopez, Robin Tharakan, Daniella Bianchi-Frias, Ruth F Dumpit, Arja Kaipainen, Alexandra N Corella, Yu Chi Yang, Michael D Nyquist, Elahe Mostaghel, Andrew C Hsieh, Xiaotun Zhang, Eva Corey, Lisha G Brown, Holly M Nguyen, Kenneth Pienta, Michael Ittmann, Michael Schweizer, Lawrence D True, David Wise, Paul S Rennie, Robert L Vessella, Colm Morrissey, Peter S Nelson
Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28993502/cardiovascular-effects-of-renal-distal-tubule-deletion-of-the-fgf-receptor-1-gene
#3
Xiaobin Han, Jed Ross, Ganesh Kolumam, Min Pi, Junichiro Sonoda, Gwendalyn King, L Darryl Quarles
The bone-derived hormone fibroblast growth factor-23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1(DT-cKO) mice) resulted in left ventricular hypertrophy (LVH) and decreased kidney expression of α-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na(+)-K(+)-2Cl(-) cotransporter...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28990606/a-combined-docosahexaenoic-acid-thyroid-hormone-protocol-upregulates-rat-liver-%C3%AE-klotho-expression-and-downstream-components-of-fgf21-signaling-as-a-potential-novel-approach-to-metabolic-stress-conditions
#4
R Vargas, B Riquelme, J Fernández, L A Videla
Liver preconditioning by a docosahexaenoic acid (DHA) and triiodothyronine (T3) combined protocol underlies peroxisome-proliferator activated receptor α (PPARα)-fibroblast growth factor 21 (FGF21) upregulation, the study of the regulatory mechanisms involved being the aim of this work. Combined DHA (daily doses of 300 mg kg(-1) for 3 days)-T3 (0.05 mg kg(-1) at the fourth day) administration elicited higher levels of liver DHA and serum T3, with enhanced hepatic nuclear/cytosolic PPARα ratios, upregulation of FGF21 and β-Klotho expression, and a small reduction in that of FGF receptor 1 (FGFR1), compared with the respective controls...
October 9, 2017: Food & Function
https://www.readbyqxmd.com/read/28988823/fgf19-fgf21-and-an-fgfr1-%C3%AE-klotho-activating-antibody-act-on-the-nervous-system-to-regulate-body-weight-and-glycemia
#5
Tian Lan, Donald A Morgan, Kamal Rahmouni, Junichiro Sonoda, Xiaorong Fu, Shawn C Burgess, William L Holland, Steven A Kliewer, David J Mangelsdorf
Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor β-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28977611/peptide-based-regulation-of-metabolism-as-related-to-obesity
#6
Werner G Bergen
Currently there are few, if any, approved and effective medicines for the attenuation of obesity, diabetes, and insulin resistance. This commentary addresses a communication describing the effect on glucose dynamics and obesity of a peptide monoclonal antibody for fibroblast growth factor (FGF) receptor 1c isoform (FGFR1c). The general lack of suitable, effective drugs is discussed, as is the treatment potential of FGF family receptors. The FGFR1c monoclonal antibody developed by the authors lowers body weight gain, blood glucose, and adipose tissue weight...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28972999/effects-of-insulin-like-growth-factors-on-early-embryonic-chick-limb-myogenesis
#7
Rabeea Hazim Mohammed, Helen Anderton, John Michael Brameld, Dylan Sweetman
Limb muscles derive from pax3 expressing precursor cells that migrate from the hypaxial somite into the developing limb bud. Once there they begin to differentiate and express muscle determination genes such as MyoD. This process is regulated by a combination of inductive or inhibitory signals including Fgf18, retinoic acid, HGF, Notch and IGFs. IGFs are well known to affect late stages of muscle development and to promote both proliferation and differentiation. We examined their roles in early stage limb bud myogenesis using chicken embryos as an experimental model...
2017: PloS One
https://www.readbyqxmd.com/read/28971553/evaluation-of-fibroblast-growth-factor-activity-exerted-by-placental-extract-used-as-a-cosmetic-ingredient
#8
Kouhei Ito, Ryuji Yamada, Nobuki Matsumoto, Toru Imamura
BACKGROUND: The biological activities claimed for placental extract (PE) in its medical and cosmetic applications are largely assumed to be the combined effects of its various signaling molecules and nutritional constituents. But there are considerable uncertainties about this assumption. AIMS: To determine the specific biological activity of PE at a molecular level. METHODS: Fibroblast growth factor (FGF) activity was assessed based on the ability to induce proliferation of FGF receptor (FGFR)-overexpressing BaF3 cells...
October 2, 2017: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/28968431/breast-cancer-cell-derived-fibroblast-growth-factors-enhance-osteoclast-activity-and-contribute-to-the-formation-of-metastatic-lesions
#9
Kelly Aukes, Cynthia Forsman, Nicholas J Brady, Kristina Astleford, Nicholas Blixt, Deepali Sachdev, Eric D Jensen, Kim C Mansky, Kathryn L Schwertfeger
Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been implicated in promoting breast cancer growth and progression. While the autocrine effects of FGFR activation in tumor cells have been extensively studied, little is known about the effects of tumor cell-derived FGFs on cells in the microenvironment. Because FGF signaling has been implicated in the regulation of bone formation and osteoclast differentiation, we hypothesized that tumor cell-derived FGFs are capable of modulating osteoclast function and contributing to growth of metastatic lesions in the bone...
2017: PloS One
https://www.readbyqxmd.com/read/28964968/dephosphorylation-is-the-mechanism-of-fibroblast-growth-factor-inhibition-of-guanylyl-cyclase-b
#10
Jerid W Robinson, Jeremy R Egbert, Julia Davydova, Hannes Schmidt, Laurinda A Jaffe, Lincoln R Potter
Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations of guanylyl cyclase-B (GC-B, also called NPRB or NPR2) cause dwarfism. FGF exposure inhibits GC-B activity in a chondrocyte cell line, but the mechanism of the inactivation is not known. Here, we report that FGF exposure causes dephosphorylation of GC-B in rat chondrosarcoma cells, which correlates with a rapid, potent and reversible inhibition of C-type natriuretic peptide-dependent activation of GC-B. Cells expressing a phosphomimetic mutant of GC-B that cannot be inactivated by dephosphorylation because it contains glutamate substitutions for all known phosphorylation sites showed no decrease in GC-B activity in response to FGF...
September 28, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28963390/acromegaly-with-hypophosphataemia-mccune-albright-syndrome
#11
Rimesh Pal, Pinaki Dutta, Kanchan Kumar Mukherjee, Anil Bhansali
A 38-year-old man presented with excessive height gain and progressive enlargement of the extremities since childhood. This was compounded by lower limb deformities over the past 5 years. On examination, his height was 196 cm, he had macroglossia, acral enlargement, seborrhoea, hyperhidrosis-suggesting acrogigantism. He had facial asymmetry, wind-swept deformity of lower limbs and a café-au-lait macule over his trunk. Investigations revealed normal-sized pituitary gland with dysplastic cranial bones. Isotope bone scintigraphy was suggestive of polyostotic fibrous dysplasia...
September 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28954993/regorafenib-induces-adaptive-resistance-of-colorectal-cancer-cells-via-inhibition-of-vascular-endothelial-growth-factor-receptor
#12
Chisato Tomida, Hikaru Nagano, Naoko Yamagishi, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28948552/adipokine-and-cytokine-profiles-of-epicardial-and-subcutaneous-adipose-tissue-in-patients-with-coronary-heart-disease
#13
O V Gruzdeva, O E Akbasheva, Yu A Dyleva, L V Antonova, V G Matveeva, E G Uchasova, E V Fanaskova, V N Karetnikova, S V Ivanov, O L Barbarash
The content of adipokines, pro- and anti-inflammatory cytokines were studied in adipocytes isolated from epicardial and subcutaneous adipose tissue of 24 coronary heart disease patients. The content of leptin and soluble leptin receptor in adipocytes of epicardial adipose tissue was higher by 28.6 and 56.9% and the level of adiponectin was lower by 33% than in adipocytes of the subcutaneous fat. In culture of epicardial adipocytes, the levels of proinflammatory cytokines TNF-α and IL-1 were higher. Subcutaneous adipose tissue adipocytes were characterized by higher levels of anti-inflammatory cytokines IL-10 and FGF-β...
September 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28947594/mir-339-inhibits-proliferation-of-pulmonary-artery-smooth-muscle-cell-by-targeting-fgf-signaling
#14
Jidong Chen, Xiaolei Cui, Li Li, Junle Qu, J Usha Raj, Deming Gou
Pulmonary artery hypertension (PAH) is a fatal disorder. Recent studies suggest that microRNA (miRNA) plays an important role in regulating proliferation of pulmonary artery smooth muscle cells (PASMC), which underlies the pathology of PAH However, the exact mechanism of action of miRNAs remains elusive. In this study, we found that miR-339 was highly expressed in the cardiovascular system and was downregulated by a group of cytokines and growth factors, especially PDGF-BB and FGF2. Functional analyses revealed that miR-339 can inhibit proliferation of PASMC Also, miR-339 inhibited FGF2-induced proliferation, but had no effect on proliferation induced by PDGF-BB The fibroblast growth factor receptor substrate 2 (FRS2) was identified as a potential direct target of miR-339...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28938541/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#15
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938491/inhibition-of-fgfr-signaling-partially-rescues-hypophosphatemic-rickets-in-hmwfgf2-tg-male-mice
#16
Liping Xiao, Erxia Du, Collin Homer-Bouthiette, Marja M Hurley
Transgenic mice harboring high molecular weight fibroblast growth factor (FGF)2 isoforms (HMWTg) in osteoblast lineage cells phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets. Because HMWFGF2 was upregulated in bones of Hyp mice and abnormal FGF receptor (FGFR) signaling is important in XLH, HMWTg mice were used to examine the effect of the FGFR inhibitor NVP-BGJ398, now in clinical trials for cancer therapy, on hypophosphatemic rickets...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938467/testis-determination-requires-a-specific-fgfr2-isoform-to-repress-foxl2
#17
Stefan Bagheri-Fam, Anthony D Bird, Liang Zhao, Janelle M Ryan, Meiyun Yong, Dagmar Wilhelm, Peter Koopman, Jacob V Eswarakumar, Vincent R Harley
Male sex determination in mammals relies on SRY-mediated up-regulation of SOX9 expression in XY gonads, whereas WNT/RSPO signalling and FOXL2 drive female sex determination in XX gonads. FGF9-signalling ensures sustained SOX9 expression through repression of one of the ovarian pathways (WNT signalling), while the significance of FGF-mediated repression of the FOXL2 pathway has not been studied. Previously, we demonstrated that FGFR2 is the receptor for FGF9 in the XY gonad. Whether a specific isoform (FGFR2b or FGFR2c) is required was puzzling...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28937875/multiplex-cytokine-analysis-of-aqueous-humor-from-the-patients-with-chronic-primary-angle-closure-glaucoma
#18
Roopam Duvesh, George Puthuran, Kavitha Srinivasan, Venkatesh Rengaraj, S R Krishnadas, Sharmila Rajendrababu, Vijayakumar Balakrishnan, Pradeep Ramulu, Periasamy Sundaresan
PURPOSE: To compare the levels of cytokines and growth factor in aqueous humor of the patients with chronic primary angle closure glaucoma (PACG) and cataract. METHODS: Aqueous humor samples were collected from 19 chronic PACG patients and compared with 14 nonglaucomatous controls presenting for cataract surgery. The levels of 27 cytokines and growth factors were measured in the aqueous samples using multiplex bead immunoassay and compared across groups. RESULTS: Significantly higher levels of interleukin (IL)-8 (p < 0...
September 22, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28928847/anti-angiogenic-effect-of-arsenic-trioxide-in-lung-cancer-via-inhibition-of-endothelial-cell-migration-proliferation-and-tube-formation
#19
Meng-Hang Yang, Ke-Jie Chang, Jin-Cheng Zheng, Hai Huang, Guang-Yuan Sun, Xue-Wei Zhao, Bing Li, Qing-Yu Xiu
Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927233/fibroblast-growth-factor-2-mediated-fgfr-erk-signaling-supports-maintenance-of-cancer-stem-like-cells-in-esophageal-squamous-cell-carcinoma
#20
Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Shunsuke Ohnishi, Yoshito Komatsu, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Tomoe Shimazaki, Megumi Kimura, Ayaka Asano, Yoshiyuki Fujimoto, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Kelly A Whelan, Hiroshi Nakagawa, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression of CD44 and low expression of CD24 has been reported to possess characteristics of cancer stem-like cells (CSCs). Novel therapies directly targeting CSCs have the potential to improve prognosis of ESCC patients. Although fibroblast growth factor-2 (FGF-2) expression correlates with recurrence and poor survival in ESCC patients, the role of FGF-2 in regulation of ESCC CSCs has yet to be elucidated. We report that FGF-2 is significantly upregulated in CSCs and significantly increases CSC content in ESCC cell lines by inducing epithelial-mesenchymal transition (EMT)...
September 13, 2017: Carcinogenesis
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