Unknown

Dataset Information

0

Sprouty1 induces a senescence-associated secretory phenotype by regulating NF?B activity: implications for tumorigenesis.


ABSTRACT: Genes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinase (RTK) signaling. As such, they restrain proliferation of many cell types and have been proposed as tumor-suppressor genes. Although their most widely accepted target is the Extracellular-regulated kinases (ERK) pathway, the mechanisms by which Spry proteins inhibit RTK signaling are poorly understood. In the present work, we describe a novel mechanism by which Spry1 restricts proliferation, independently of the ERK pathway. In vivo analysis of thyroid glands from Spry1 knockout mice reveals that Spry1 induces a senescence-associated secretory phenotype via activation of the NF?B pathway. Consistently, thyroids from Spry1 knockout mice are bigger and exhibit decreased markers of senescence including Ki67 labeling and senescence-associated ?-galactosidase. Although such 'escape' from senescence is not sufficient to promote thyroid tumorigenesis in adult mice up to 5 months, the onset of Phosphatase and tensin homolog (Pten)-induced tumor formation is accelerated when Spry1 is concomitantly eliminated. Accordingly, we observe a reduction of SPRY1 levels in human thyroid malignancies when compared with non-tumoral tissue. We propose that Spry1 acts as a sensor of mitogenic activity that not only attenuates RTK signaling but also induces a cellular senescence response to avoid uncontrolled proliferation.

SUBMITTER: Macia A 

PROVIDER: S-EPMC3890957 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Sprouty1 induces a senescence-associated secretory phenotype by regulating NFκB activity: implications for tumorigenesis.

Macià A A   Vaquero M M   Gou-Fàbregas M M   Castelblanco E E   Valdivielso J M JM   Anerillas C C   Mauricio D D   Matias-Guiu X X   Ribera J J   Encinas M M  

Cell death and differentiation 20131122 2


Genes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinase (RTK) signaling. As such, they restrain proliferation of many cell types and have been proposed as tumor-suppressor genes. Although their most widely accepted target is the Extracellular-regulated kinases (ERK) pathway, the mechanisms by which Spry proteins inhibit RTK signaling are poorly understood. In the present work, we describe a novel mechanism by which Spry1 restricts proliferation, independently of  ...[more]

Similar Datasets

| S-EPMC4749409 | biostudies-literature
| S-EPMC5322731 | biostudies-literature
| S-EPMC6981212 | biostudies-literature
| S-EPMC7795172 | biostudies-literature
| S-EPMC3196093 | biostudies-literature
| S-EPMC8502980 | biostudies-literature
| S-EPMC7032038 | biostudies-literature
| S-EPMC3936307 | biostudies-literature
| S-EPMC7906185 | biostudies-literature
| S-EPMC4743061 | biostudies-literature