scholarly journals Amphiregulin Regulates Melanocytic Senescence

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 326
Author(s):  
Michaela Pommer ◽  
Silke Kuphal ◽  
Anja K. Bosserhoff
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Development ◽  
Growth Factor Receptor ◽  
Senescent Cell ◽  
Braf V600e ◽  
Molecular Component ◽  
Egfr Ligands ◽  
Epidermal Growth

Oncogene-induced senescence (OIS) is a decisive process to suppress tumor development, but the molecular details of OIS are still under investigation. Using an established OIS model of primary melanocytes transduced with BRAF V600E and compared to control cells, amphiregulin (AREG) was shown to be induced. In addition, AREG expression was observed in nevi, which by definition, are senescent cell clusters, compared to melanocytes. Interestingly, treatment of melanocytes with recombinant AREG did induce senescence. This led to the assumption that extracellular AREG has an important function in this process. Inhibition of the epidermal growth factor receptor (EGFR) using Gefitinib identified AREG as one of EGFR ligands responsible for senescence. Furthermore, depletion of AREG expression in senescent BRAF V600E melanocytes resulted in a significant reduction of senescent melanocytes. This study reveals AREG as an essential molecular component of signaling pathways leading to senescence in melanocytes.

scholarly journals Substrate Selectivity of Epidermal Growth Factor-Receptor Ligand Sheddases and their Regulation by Phorbol Esters and Calcium Influx

2007 ◽  
Vol 18 (1) ◽  
pp. 176-188 ◽  
Author(s):  
Keisuke Horiuchi ◽  
Sylvain Le Gall ◽  
Marc Schulte ◽  
Takafumi Yamaguchi ◽  
Karina Reiss ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phorbol Esters ◽  
Calcium Influx ◽  
Growth Factor Receptor ◽  
Egfr Ligands ◽  
Egfr Ligand ◽  
Epidermal Growth ◽  
Ligand Shedding

Signaling via the epidermal growth factor receptor (EGFR), which has critical roles in development and diseases such as cancer, is regulated by proteolytic shedding of its membrane-tethered ligands. Sheddases for EGFR-ligands are therefore key signaling switches in the EGFR pathway. Here, we determined which ADAMs (a disintegrin and metalloprotease) can shed various EGFR-ligands, and we analyzed the regulation of EGFR-ligand shedding by two commonly used stimuli, phorbol esters and calcium influx. Phorbol esters predominantly activate ADAM17, thereby triggering a burst of shedding of EGFR-ligands from a late secretory pathway compartment. Calcium influx stimulates ADAM10, requiring its cytoplasmic domain. However, calcium influx-stimulated shedding of transforming growth factor α and amphiregulin does not require ADAM17, even though ADAM17 is essential for phorbol ester-stimulated shedding of these EGFR-ligands. This study provides new insight into the machinery responsible for EGFR-ligand release and thus EGFR signaling and demonstrates that dysregulated EGFR-ligand shedding may be caused by increased expression of constitutively active sheddases or activation of different sheddases by distinct stimuli.

scholarly journals Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3200
Author(s):  
Thomas Frawley ◽  
Olga Piskareva
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Tumour Cells ◽  
Egfr Ligands ◽  
Epidermal Growth ◽  
Bio Engineering ◽  
Mutant Egfr

The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These oncogenic effects were thought to be confined to aberrant cells hosting genetic alterations in EGFR. However, in the past decade, numerous studies identified that tumour cells could harness extracellular vesicles (EVs) to disseminate EGFR, mutant EGFR, phosphorylated EGFR and EGFR ligands to local and distant cells. This functions to impart a pro-tumourigenic phenotype in recipient cells. EVs play an essential role in intracellular communication, through receptor signalling or the release of their intra-vesicular content into recipient cells. This review will discuss the role of EVs delivering EGFR or EGFR ligands either to or from tumour cells and how this can promote metastases, pre-metastatic niche formation, osteoclastogenesis, angiogenesis and immune modulation in cancer. We will examine how circulating EVs positive for EGFR may be exploited as diagnostic, prognostic or therapeutic markers in cancers including breast, lung, glioblastoma, ovarian and prostate. Finally, we will explore recent breakthroughs in bio-engineering EVs with EGFR targeting abilities for targeted drug delivery.

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