Bimodal expression of Sprouty2 during the cell cycle is mediated by phase-specific Ras/MAPK and c-Cbl activities

Mayer, Christoph-Erik; Haigl, Barbara; Jantscher, Florian; Siegwart, Gerald; Grusch, Michael; Berger, Walter; Sutterlüty, Hedwig

doi:10.1007/s00018-010-0379-6

Cited by 17 publications

(13 citation statements)

References 49 publications

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“…Thus, Spry2 accumulates to higher levels and inhibits FGF-induced signaling more efficiently in c-Cbl-null mouse embryonic fibroblasts (MEFs) than in control MEFs [89, 90]. Reporting bimodal expression of Spry2 along with sustained elevation of Spry4 during cell cycle progression, Mayer et al [91] indicated that second phase in the expression profile of Spry2 as transient attenuation of the protein expression during late G1 is solely dependent on cell cycle-specific ubiquitination by c-Cbl. DaSilva et al [92] showed that serine phosphorylation on Ser112 and Ser121 by MAPK-interacting kinase 1 (Mnk1) provides Spry2 with balanced phosphorylation of Tyr55 that leads to the protein stabilization.…”

Section: Sprouty: a Versatile Modulator With Complex Functionalitymentioning

confidence: 99%

The developing story of Sprouty and cancer

Masoumi-Moghaddam

Amini

Morris

2014

Cancer Metastasis Rev

139

181

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Sprouty proteins are evolutionarily conserved modulators of MAPK/ERK pathway. Through interacting with an increasing number of effectors, mediators, and regulators with ultimate influence on multiple targets within or beyond ERK, Sprouty orchestrates a complex, multilayered regulatory system and mediates a crosstalk among different signaling pathways for a coordinated cellular response. As such, Sprouty has been implicated in various developmental and physiological processes. Evidence shows that ERK is aberrantly activated in malignant conditions. Accordingly, Sprouty deregulation has been reported in different cancer types and shown to impact cancer development, progression, and metastasis. In this article, we have tried to provide an overview of the current knowledge about the Sprouty physiology and its regulatory functions in health, as well as an updated review of the Sprouty status in cancer. Putative implications of Sprouty in cancer biology, their clinical relevance, and their proposed applications are also revisited. As a developing story, however, role of Sprouty in cancer remains to be further elucidated.

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Section: Sprouty: a Versatile Modulator With Complex Functionalitymentioning

confidence: 99%

The developing story of Sprouty and cancer

Masoumi-Moghaddam

Amini

Morris

2014

Cancer Metastasis Rev

139

181

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“…Synchronization of cells in certain phases of the cell cycle was achieved by serum starvation as described (21). Propidium iodide-based DNA content analysis (PI-staining) was performed as described (22).…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as described (21). Primary antibodies against β-actin (Novus Biologicals, CO, USA) and Au5 epitope (Bethyl Laboratories, TX, USA) were used.…”

Section: Methodsmentioning

confidence: 99%

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Expression of microRNA-21 in non-small cell lung cancer tissue increases with disease progression and is likely caused by growth conditional changes during malignant transformation

Haigl

Vanas

Setinek

et al. 2014

International Journal of Oncology

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Abstract. MicroRNAs can govern up to hundred different mRNAs and are important regulators of gene expression programs in development and disease. We analyzed the expression of microRNA-21, one of the most common oncomirs, in non-small cell lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of NSCLC-derived tissue and cell lines were measured. In line with earlier observations we show that mature microRNA-21 expression levels are highly increased in NSCLC-derived tissue compared to normal lung tissue. Additionally, we demonstrate that microRNA-21 levels correlate with malignancy since its expression in higher staged tumors is significantly more elevated compared to stage 1A. Interestingly, microRNA-21 levels in cultured NSCLC-derived cells are comparable to the expression detected in non-malignant lung tissue. Since microRNA-21 levels showed no fluctuation during the cell cycle, accelerated proliferation of tumor cells is not responsible for microRNA-21 upregulation in the tumor compartment. Similarly to NSCLC-derived cancer cells, the tumor-associated fibroblasts show low expression levels of microRNA-21. Together, these data indicate that rather microenviromental and growth conditional changes than intrinsic features of the cancer cells are responsible for the observed increase of microRNA-21 levels in tumor tissues. Subsequently culturing conditions were changed to assess the impact of co-cultivation with fibroblasts, hypoxia and anchorage-independent growth on microRNA-21 expression. While co-cultivation with tumor-associated fibroblasts had no effect on microRNA-21 expression, both hypoxia and anchorage-independent growth cause a microRNA-21 elevation. In summary, our data demonstrate that growth conditions especially expected in more malignant tumors result in microRNA-21 upregulation explaining the observed increase in higher staged lung cancer tissue, but not in lung cancerderived cells.

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“…17 Also, Spry4 expression can be induced when cells are stimulated by the activation of RTK-mediated signaling via addition of epidermal growth factor (EGF), FGF2, serum or RAS expression. 15,16 Although at mRNA level, two reports describe a reduction of Spry1 levels 13,14 , whereas in another experiment, Spry1 mRNA is induced in response to growth factor addition, 18 Spry1 protein in response to growth factor activation was not investigated. The goal of this study is to examine the influence of RTK-signaling on Spry1 protein expression in tumor and normal cells of the lung.…”

Section: Introductionmentioning

confidence: 92%

In non‐small cell lung cancer mitogenic signaling leaves Sprouty1 protein levels unaffected

Kral

Mayer

Vanas

et al. 2013

Cell Biochemistry & Function

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Sprouty1 protein belongs to a family of receptor tyrosine kinase-mediated signaling inhibitors, whose members are usually regulated by growth factors to form a negative feedback loop. Correspondingly fluctuations of Sprouty1 mRNA in response to single growth factors have been observed. In this report, we investigate Sprouty1 protein levels and show that in non-small cell lung carcinoma-derived cells, the expression levels are unaffected by the serum content in the cellular environment. Although cells harboring K-Ras mutations express insignificant higher Sprouty1 levels, ectopic expression of constitutive active Ras in normal human lung fibroblasts fails to augment Sprouty1 protein content. Furthermore, serum starvation for three days has no influence on Sprouty1 expression and addition of serum or of singular growth factors leaves Sprouty protein levels unchanged. Cell cycle analysis reveals that Sprouty1 levels remain constant throughout the whole cell cycle. These data demonstrate that Sprouty1 expression is not connected with mitogenic signaling and cell proliferation.

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Bimodal expression of Sprouty2 during the cell cycle is mediated by phase-specific Ras/MAPK and c-Cbl activities

Cited by 17 publications

References 49 publications

The developing story of Sprouty and cancer

The developing story of Sprouty and cancer

Expression of microRNA-21 in non-small cell lung cancer tissue increases with disease progression and is likely caused by growth conditional changes during malignant transformation

In non‐small cell lung cancer mitogenic signaling leaves Sprouty1 protein levels unaffected

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