scholarly journals Anticancer drug targets: growth factors and growth factor signaling

2000 ◽  
Vol 105 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Jackson B. Gibbs
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Anticancer Drug ◽  
Drug Targets ◽  
Growth Factor Signaling

scholarly journals AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

2000 ◽  
Vol 20 (14) ◽  
pp. 5041-5047 ◽  
Author(s):  
Jaime Font de Mora ◽  
Myles Brown
Keyword(s):  
Estrogen Receptor ◽  
Growth Factors ◽  
Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Growth Factor Signaling ◽  
Breast Cancers ◽  
Mapk Activation ◽  
Mitogen Activated Protein

ABSTRACT Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the ligand-independent activity of ER through the activation of mitogen-activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We demonstrate that AIB1 is a phosphoprotein in vivo and can be phosphorylated in vitro by MAPK. Finally, we observed that MAPK activation of AIB1 stimulates the recruitment of p300 and associated histone acetyltransferase activity. These results suggest that the ability of growth factors to modulate estrogen action may be mediated through MAPK activation of the nuclear receptor coactivator AIB1.

scholarly journals Fibroblast Growth Factor Signaling during Early Vertebrate Development

2004 ◽  
Vol 26 (1) ◽  
pp. 63-77 ◽  
Author(s):  
Ralph T. Böttcher ◽  
Christof Niehrs
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factors ◽  
Growth Factor Signaling ◽  
Fibroblast Growth ◽  
Vertebrate Development ◽  
Fgf Signaling ◽  
Fibroblast Growth Factor Signaling ◽  
Cellular Processes ◽  
Differentiation And Proliferation

Fibroblast growth factors (FGFs) have been implicated in diverse cellular processes including apoptosis, cell survival, chemotaxis, cell adhesion, migration, differentiation, and proliferation. This review presents our current understanding on the roles of FGF signaling, the pathways employed, and its regulation. We focus on FGF signaling during early embryonic processes in vertebrates, such as induction and patterning of the three germ layers as well as its function in the control of morphogenetic movements.

Growth factor stimulation of matrix metalloproteinase expression and myoblast migration and invasion in vitro

2003 ◽  
Vol 284 (4) ◽  
pp. C805-C815 ◽  
Author(s):  
David L. Allen ◽  
Daniel H. Teitelbaum ◽  
Kotoku Kurachi
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Migration And Invasion ◽  
Growth Factor Signaling ◽  
Proteolytic Activation ◽  
Tnf Α ◽  
Promoter Construct

We investigated the role of growth factors and fibronectin on matrix metalloproteinase (MMP) expression and on migration and invasion of mouse skeletal myoblasts in vitro. None of the growth factors tested significantly affected MMP-1 or MMP-2 activity as revealed by gelatin zymography, but both basic FGF (bFGF) and tumor necrosis factor (TNF)-α significantly increased MMP-9 activity (10- and 30-fold, respectively). The increase in secreted MMP-9 activity with TNF-α stimulation was due at least in part to an increase in MMP-9 gene transcription, because an MMP-9 promoter construct was approximately fivefold more active in TNF-α-treated myoblasts than in control myoblasts, as well as an increase in MMP-9 proteolytic activation. However, whereas fibronectin, bFGF, hepatocyte growth factor, and TGF-β1 significantly augmented migration of mouse myoblasts, TNF-α did not, nor did PDGF-BB or IGF-I. Fibronectin and bFGF also significantly augmented invasion of myoblasts across a Matrigel barrier, and plasmin cotreatment potentiated whereas N-acetyl cysteine suppressed the effects of bFGF and fibronectin on myoblast migration and invasion. Finally, transient transfection with an MMP-9 overexpression construct had only minimal effects on myoblast migration/invasion, whereas overexpression of either MMP-2 or MMP-1 significantly augmented myoblast migration and invasion. These observations support the hypothesis that MMP activity is a necessary component of growth factor-mediated myoblast migration but suggest that other consequences of growth factor signaling are also necessary for migration to occur.

scholarly journals Growth factor signaling to mTORC1 by amino acid–laden macropinosomes

2015 ◽  
Vol 211 (1) ◽  
pp. 159-172 ◽  
Author(s):  
Sei Yoshida ◽  
Regina Pacitto ◽  
Yao Yao ◽  
Ken Inoki ◽  
Joel A. Swanson
Keyword(s):  
Amino Acids ◽  
Growth Factors ◽  
Amino Acid ◽  
Growth Factor ◽  
Phorbol Esters ◽  
Growth Factor Receptor ◽  
Fluid Phase ◽  
Growth Factor Signaling ◽  
Murine Bone Marrow ◽  
Rapid Activation

The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid–dependent activation of mTORC1. Here, we show that growth factor-dependent activation of mTORC1 by amino acids, but not glucose, requires macropinocytosis. In murine bone marrow–derived macrophages and murine embryonic fibroblasts stimulated with their cognate growth factors or with phorbol myristate acetate, activation of mTORC1 required an Akt-independent vesicular pathway of amino acid delivery into endolysosomes, mediated by the actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase solutes into endolysosomes sufficiently fast to explain growth factor–mediated signaling by amino acids. Therefore, the amino acid–laden macropinosome is an essential and discrete unit of growth factor receptor signaling to mTORC1.

Prediction of Anticancer Drug Potency from Expression of Genes Involved in Growth Factor Signaling

2006 ◽  
Vol 23 (2) ◽  
pp. 336-349 ◽  
Author(s):  
Zunyan Dai ◽  
Catalin Barbacioru ◽  
Ying Huang ◽  
Wolfgang Sadée
Keyword(s):  
Growth Factor ◽  
Anticancer Drug ◽  
Growth Factor Signaling ◽  
Expression Of Genes ◽  
Drug Potency

scholarly journals A spatially regulated GTPase cycle of Rheb controls growth factor signaling to mTORC1

2018 ◽  
Author(s):  
Marija Kovacevic ◽  
Christian H. Klein ◽  
Lisaweta Roßmannek ◽  
Antonios D. Konitsiotis ◽  
Angel Stanoev ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Small Gtpase ◽  
Target Of Rapamycin ◽  
Growth Factor Signaling ◽  
Nucleotide Exchange ◽  
Gtpase Activating Protein ◽  
Mechanistic Target Of Rapamycin ◽  
Gtpase Cycle ◽  
Mtorc1 Activation

ABSTRACTGrowth factors initiate anabolism by activating mechanistic target of rapamycin complex 1 (mTORC1) via the small GTPase Rheb. We show that the GTPase cycle of Rheb is spatially regulated by the interaction with its GDI-like solubilizing factor (GSF) – PDEδ. Arl2-GTP mediated localized release of cytosolic Rheb-GTP from PDEδ deposits it onto perinuclear membranes where it forms a complex with mTORC1. The membrane associated GTPase activating protein (GAP) TSC2 hydrolyzes Rheb-GTP, weakening the interaction with mTOR. Rheb-GDP is readily released into the cytosol where it is maintained soluble by interaction with PDEδ. This solubilized Rheb is re-activated by nucleotide exchange to be re-deposited by Arl2-mediated release onto perinuclear membranes. This spatial GTPase cycle thereby enables mTORC1 activation to be solely controlled by growth factor induced inactivation of TSC2. The coupling between mTOR activation and spatially regulated Rheb nucleotide exchange makes growth factor induced proliferation critically dependent on PDEδ expression.

scholarly journals Growth factor signaling predicts therapy resistance mechanisms and defines neuroblastoma subtypes

Oncogene ◽  
2021 ◽  
Author(s):  
Timofey Lebedev ◽  
Elmira Vagapova ◽  
Pavel Spirin ◽  
Petr Rubtsov ◽  
Olga Astashkova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Protective Action ◽  
Mycn Amplification ◽  
Survival Prediction ◽  
Growth Factor Signaling ◽  
Erk Activation ◽  
Multikinase Inhibitors ◽  
Recurrent Mutations

AbstractNeuroblastoma (NB) has a low frequency of recurrent mutations compared to other cancers, which hinders the development of targeted therapies and novel risk stratification strategies. Multikinase inhibitors have shown potential in treating high-risk NB, but their efficacy is likely impaired by the cancer cells’ ability to adapt to these drugs through the employment of alternative signaling pathways. Based on the expression of 48 growth factor-related genes in 1189 NB tumors, we have developed a model for NB patient survival prediction. This model discriminates between stage 4 NB tumors with favorable outcomes (>80% overall survival) and very poor outcomes (<10%) independently from MYCN-amplification status. Using signaling pathway analysis and gene set enrichment methods in 60 NB patients with known therapy response, we identified signaling pathways, including EPO, NGF, and HGF, upregulated in patients with no or partial response. In a therapeutic setting, we showed that among six selected growth factors, EPO, and NGF showed the most pronounced protective effects in vitro against several promising anti-NB multikinase inhibitors: imatinib, dasatinib, crizotinib, cabozantinib, and axitinib. Mechanistically kinase inhibitors potentiated NB cells to stronger ERK activation by EPO and NGF. The protective action of these growth factors strongly correlated with ERK activation and was ERK-dependent. ERK inhibitors combined with anticancer drugs, especially with dasatinib, showed a synergistic effect on NB cell death. Consideration of growth factor signaling activity benefits NB outcome prediction and tailoring therapy regimens to treat NB.

scholarly journals Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Simona Ceccarelli ◽  
Cristina Nodale ◽  
Enrica Vescarelli ◽  
Paola Pontecorvi ◽  
Valeria Manganelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Adipogenic Differentiation ◽  
Growth Factor Signaling ◽  
Adipose Derived Stem Cells ◽  
Transient Activation ◽  
Neuropilin 1

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.

Mechanism and Physiological Significance of Growth Factor-Related Autophagy

Physiology ◽  
2013 ◽  
Vol 28 (6) ◽  
pp. 423-431 ◽  
Author(s):  
Terytty Yang Li ◽  
Shu-Yong Lin ◽  
Sheng-Cai Lin
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Fate ◽  
Energy Homeostasis ◽  
Growth Factor Signaling ◽  
Cell Fate Determination ◽  
Natural Substances ◽  
Autophagy Induction ◽  
Cell Growth And Differentiation ◽  
Intracellular Energy

Growth factors, typically defined as natural substances capable of stimulating cell growth and differentiation, are vital regulators for the survival of metazoan cells. In this review, we will focus on growth factor signaling pathways that are closely related to autophagy induction and discuss the critical roles of this fascinating cellular process in intracellular energy homeostasis, cell fate determination, and pathophysiological regulation.

Sign in / Sign up

Export Citation Format

Share Document