scholarly journals Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia

2013 ◽  
Vol 201 (2) ◽  
pp. 279-292 ◽  
Author(s):  
Begoña Díaz ◽  
Angela Yuen ◽  
Shinji Iizuka ◽  
Shigeki Higashiyama ◽  
Sara A. Courtneidge
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Egf Receptor ◽  
Cell Contact ◽  
Dependent Manner ◽  
Heparin Binding ◽  
Cancer Cell Invasion ◽  
Cellular Invasion

Notch regulates cell–cell contact-dependent signaling and is activated by hypoxia, a microenvironmental condition that promotes cellular invasion during both normal physiology and disease. The mechanisms by which hypoxia and Notch regulate cellular invasion are not fully elucidated. In this paper, we show that, in cancer cells, hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling–dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. Released HB-EGF induced the formation of invadopodia, cellular structures that aid cancer cell invasion. Thus, we describe a signaling pathway that couples cell contact–dependent signaling with the paracrine activation of the EGFR, indicating cross talk between the Notch and EGFR pathways in promoting cancer cell invasion. This signaling pathway might regulate the coordinated acquisition of invasiveness by neighboring cells and mediate the communication between normoxic and hypoxic areas of tumors to facilitate cancer cell invasion.

scholarly journals Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

2006 ◽  
Vol 13 (4) ◽  
pp. 1173-1183 ◽  
Author(s):  
Michael W Yeh ◽  
Jean-Philippe Rougier ◽  
Jin-Woo Park ◽  
Quan-Yang Duh ◽  
Mariwil Wong ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Thyroid Cancer ◽  
Growth Factor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Growth Factor Receptor ◽  
Thyroid Cancer Cell ◽  
Cancer Cell Invasion ◽  
Epidermal Growth

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P < 0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64- to 8.89-fold, P < 0.0001) and membrane type-1 MMP (MT1-MMP, 1.97- to 2.67-fold, P < 0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.

scholarly journals The RhoA dependent anti-metastatic function of RKIP in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gardiyawasam Kalpana ◽  
Christopher Figy ◽  
Jingwei Feng ◽  
Claire Tipton ◽  
Julius N. De Castro ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Rho Gtpases ◽  
Kinase Inhibitor ◽  
Cell Movement ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Cytoskeleton Dynamics

AbstractRaf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.

scholarly journals Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2-ERK1/2 signaling pathway

2006 ◽  
Vol 5 (12) ◽  
pp. 3285-3293 ◽  
Author(s):  
Siyuan Zhang ◽  
Zhi Li ◽  
Ximei Wu ◽  
Qing Huang ◽  
Han-Ming Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion

scholarly journals Livin regulates prostate cancer cell invasion by impacting the NF-κB signaling pathway and the expression of FN and CXCR4

IUBMB Life ◽  
2012 ◽  
Vol 64 (3) ◽  
pp. 274-283 ◽  
Author(s):  
Feng Chen ◽  
Deyong Yang ◽  
Shujing Wang ◽  
Xiangyu Che ◽  
Jianbo Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Prostate Cancer Cell ◽  
Cancer Cell Invasion
Sign in / Sign up

Export Citation Format

Share Document