scholarly journals Phosphorylation of adducin-1 by cyclin-dependent kinase 5 is important for epidermal growth factor-induced cell migration

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chia-Yi Su ◽  
Ruei-Liang Yan ◽  
Wen-Hsin Hsu ◽  
Ching-Tung Chu ◽  
Hsuan-Chia Chang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Cyclin Dependent Kinase ◽  
Cell Migration And Invasion ◽  
Epidermal Growth ◽  
Cyclin Dependent Kinase 5 ◽  
Lamellipodia Formation

Abstract Cyclin-dependent kinase 5 (Cdk5) is predominantly expressed in neuron and plays an important role in neuronal physiology. Increasing evidence also indicates that Cdk5 may contribute to malignant progression of some types of cancers; however, the underlying mechanism remains elusive. In this study, we found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. The capability of the phosphomimetic T724D mutant to bind to actin filaments was lower than that of wild type ADD1 and the T724A mutant. Cdk5 co-localized with ADD1 at the lamellipodia upon epidermal growth factor (EGF) stimulation. The increased lamellipodia formation and cell migration of human breast cancer cells MDA-MB-231 by EGF were accompanied by Cdk5 activation and increased phosphorylation of ADD1 at T724. Depletion of Cdk5 in MDA-MB-231 cells abrogated the effects of EGF on ADD1 T724 phosphorylation, lamellipodia formation, and cell migration. Likewise, depletion of ADD1 suppressed the effects of EGF on lamellipodia formation, cell migration, and invasion, all of which were restored by FLAG-ADD1 WT and the T724D mutant, but not the T724A mutant. Together, our results suggest that phosphorylation of ADD1 at T724 by Cdk5 is important for EGF-induced cell migration and invasion.

scholarly journals Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion

2011 ◽  
Vol 300 (5) ◽  
pp. G749-G760 ◽  
Author(s):  
Angelica Belo ◽  
Kunrong Cheng ◽  
Ahmed Chahdi ◽  
Jasleen Shant ◽  
Guofeng Xie ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Muscarinic Receptor ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Threefold Increase ◽  
Epidermal Growth

Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion.

scholarly journals Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10

2006 ◽  
Vol 395 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Toshiyuki Murai ◽  
Takayuki Miyauchi ◽  
Toshio Yanagida ◽  
Yasushi Sako
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Tumour Cell ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Dominant Negative Mutant ◽  
Mitogen Activated Protein ◽  
Epidermal Growth

Invasive tumour cells, such as gliomas, frequently express EGF (epidermal growth factor) receptor at a high level and they exhibit enhanced cell migration in response to EGF. We reported previously that tumour cell migration is associated with ectodomain cleavage of CD44, the major adhesion molecule that is implicated in tumour invasion and metastasis, and that the cleavage is enhanced by ligation of CD44. In the present study, we show that EGF promotes CD44 cleavage and CD44-dependent cell migration. Introduction of a dominant-negative mutant of the small GTPase Rac1 or depletion of Rac1 by RNAi (RNA interference) abrogated CD44 cleavage induced by EGF. Treatment with PD98059, an inhibitor for MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase), also suppressed the CD44 cleavage. Furthermore, RNAi studies showed that EGF induced ADAM10 (a disintegrin and metalloproteinase 10)-dependent CD44 cleavage and cell migration. These results indicate that EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion.

scholarly journals Epidermal Growth Factor-Like Domain-8 (EGFL8) in Mammals: The Story so far

2020 ◽  
Vol 1 (3) ◽  
pp. 3
Author(s):  
Fazli Subhan ◽  
Muhammad Naeem ◽  
Wasim Sajjad ◽  
Liaqat Ali ◽  
Isfahan Tauseef ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Notch Signaling ◽  
Current Knowledge ◽  
Migration And Invasion ◽  
Vascular Endothelial ◽  
Amino Terminal ◽  
Epidermal Growth

Epidermal growth factor-like domain-8 (EGFL8) also known as vascular endothelial statin-2 (VE-statin-2). It was identified by using retroviral gene entrapment vectors, expressed in endothelial cells. It is located on chromosome6inhumansandchromosome17inthemouse. EGFL8codesaproteinof293aminoacidswithan amino-terminal signal peptide and has two EGF-like domains. EGFL8 plays a very important regulatory role in thymopoiesis, cell migration and invasion through the modulation of Notch signaling. Although the signaling regulatory factors of EGFL8 need to be explored but recent scientific advances have revealed some important aspect of its regulation. This review summarizes the current knowledge about all aspects of EGFL8 since its discovery.

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