scholarly journals IER2-induced senescence drives melanoma invasion through osteopontin

Oncogene ◽  
2021 ◽  
Author(s):  
Lenka Kyjacova ◽  
Rafael Saup ◽  
Kerstin Rönsch ◽  
Sabine Wallbaum ◽  
Stefanie Dukowic-Schulze ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Functional Role ◽  
Early Response ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Response Gene ◽  
Early Response Gene ◽  
Melanoma Invasion

AbstractExpression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence.

Transcriptional induction of the murine c-rel gene with serum and phorbol-12-myristate-13-acetate in fibroblasts

1989 ◽  
Vol 9 (11) ◽  
pp. 5239-5243
Author(s):  
P Bull ◽  
T Hunter ◽  
I M Verma
Keyword(s):  
Steady State ◽  
Gene Family ◽  
Early Response ◽  
Response Gene ◽  
Early Response Gene ◽  
3T3 Fibroblasts ◽  
Steady State Levels ◽  
Nih 3T3 ◽  
Transcriptional Induction

Transcription of the c-rel proto-oncogene was induced transiently when resting mouse NIH 3T3 fibroblasts were stimulated with serum or phorbol-12-myristate-13-acetate. Addition of cycloheximide increased the steady-state levels of c-rel mRNA. These results indicate that c-rel is another member of the early-response gene family.

scholarly journals Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3)

Haematologica ◽  
2013 ◽  
Vol 99 (2) ◽  
pp. 282-291 ◽  
Author(s):  
H. Ramsey ◽  
Q. Zhang ◽  
D. E. Brown ◽  
D. P. Steensma ◽  
C. P. Lin ◽  
...  
Keyword(s):  
Early Response ◽  
Immediate Early ◽  
Response Gene ◽  
Early Response Gene

A novel Xenopus mix-like gene milk involved in the control of the endomesodermal fates

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2577-2585 ◽  
Author(s):  
V. Ecochard ◽  
C. Cayrol ◽  
S. Rey ◽  
F. Foulquier ◽  
D. Caillol ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Early Response ◽  
Response Gene ◽  
Mesodermal Cell ◽  
Early Response Gene ◽  
Mesoderm Formation ◽  
Definition Of ◽  
Early Gastrula

Here we describe a novel Xenopus homeobox gene, milk, related by sequence homology and expression pattern to the vegetally expressed Mix.1. As is the case with Mix.1, milk is an immediate early response gene to the mesoderm inducer activin. milk is expressed at the early gastrula stage in the vegetal cells, fated to form endoderm, and in the marginal zone fated to form mesoderm. During gastrulation, expression of milk becomes progressively reduced in the involuting mesodermal cells but is retained in the endoderm, suggesting that it may play a key role in the definition of the endo-mesodermal boundary in the embryo. Overexpression of milk in the marginal zone blocks mesodermal cell involution, represses the expression of several mesodermal genes such as Xbra, goosecoid, Xvent-1 or Xpo and increases the expression of the endodermal gene, endodermin. In the dorsal marginal zone, overexpression of milk leads to a severe late phenotype including the absence of axial structures. Ectopic expression of milk in the animal hemisphere or in ectodermal explants induces a strong expression of endodermin. Taken together, we propose that milk plays a role in the correct patterning of the embryo by repressing mesoderm formation and promoting endoderm identity.

Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells

1990 ◽  
Vol 10 (10) ◽  
pp. 5324-5332
Author(s):  
J Szeberényi ◽  
H Cai ◽  
G M Cooper
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Morphological Differentiation ◽  
Early Response ◽  
Secondary Response ◽  
Response Gene ◽  
Early Response Gene ◽  
Early Response Genes

A dominant inhibitory mutation of Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21 (Asn-17)Ha-ras] has been used to investigate the role of ras in neuronal differentiation of PC12 cells. The growth of PC12 cells, in contrast to NIH 3T3 cells, was not inhibited by p21(Asn-17)Ha-ras expression. However, PC12 cells expressing the mutant Ha-ras protein showed a marked inhibition of morphological differentiation induced by nerve growth factor (NGF) or fibroblast growth factor (FGF). These cells, however, were still able to respond with neurite outgrowth to dibutyryl cyclic AMP and 12-O-tetradecanoylphorbol-13-acetate (TPA). Induction of early-response genes (fos, jun, and zif268) by NGF and FGF but not by TPA was also inhibited by high levels of p21(Asn-17)Ha-ras. However, lower levels of p21(Asn-17) expression were sufficient to block neuronal differentiation without inhibiting induction of these early-response genes. Induction of the secondary-response genes SCG10 and transin by NGF, like morphological differentiation, was inhibited by low levels of p21(Asn-17) whether or not induction of early-response genes was blocked. Therefore, although inhibition of ras function can inhibit early-response gene induction, this is not required to block morphological differentiation or secondary-response gene expression. These results suggest that ras proteins are involved in at least two different pathways of signal transduction from the NGF receptor, which can be distinguished by differential sensitivity to p21(Asn-17)Ha-ras. In addition, ras and protein kinase C can apparently induce early-response gene expression by independent pathways in PC12 cells.

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