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

Kral, Rosana; Mayer, Christoph-Erik; Vanas, Vanita; Gsur, Andrea; Sutterlüty, Hedwig

doi:10.1002/cbf.2976

Cited by 11 publications

(13 citation statements)

References 25 publications

(34 reference statements)

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“…Protein isolation and immunoblotting were carried out as described [ 26 ]. Spry-specific antibodies were produced earlier [ 23 , 26 , 27 ] as described [ 27 ]. Antibodies recognizing PDCD4 (monoclonal, rabbit antibody EPR3431 from Epitomics was diluted 1:5000) and PTEN (monoclonal rabbit antibody EPR4408 from Epitomics was diluted 1:1000) were purchased.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells

et al. 2016

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Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells

et al. 2016

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“…Immunoblotting was carried out as described [23] using affinity purified antibodies against the NH 2 ‐terminus of Spry2 (characterised in [16]) and Spry4 (described in [24]). As a loading control primary antibodies against β‐actin (Novus Biologicals) were used.…”

Section: Methodsmentioning

confidence: 99%

Sprouty2 but not Sprouty4 is a potent inhibitor of cell proliferation and migration of osteosarcoma cells

et al. 2013

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a b s t r a c tAs negative regulators of receptor tyrosine kinase-mediated signalling, Sprouty proteins fulfil important roles during carcinogenesis. In this report, we demonstrate that Sprouty2 protein expression inhibits cell proliferation and migration in osteosarcoma-derived cells. Although earlier reports describe a tumour-promoting function, these results indicate that Sprouty proteins also have the potential to function as tumour suppressors in sarcoma. In contrast to Sprouty2, Sprouty4 expression failed to interfere with proliferation and migration of the osteosarcoma-derived cells, possibly due to a less pronounced interference with mitogen-activated protein kinase activity. Sequences within the NH 2 -terminus are responsible for the specific inhibitory function of Sprouty2 protein.

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“…Parallel studies consistently reported that the expression of Spry2 and Spry4 was rapidly induced by growth factors in fibroblasts [5], endothelial cells [6], and HEK293 cells [60], yet concomitant downregulation of Spry1 was observed [5, 6]. Moreover, Kral et al [79] demonstrated that neither growth factor stimulation nor Ras activation increased the Spry1 protein levels in WI38 normal human lung fibroblasts. Since Spry1 in their cell cycle analysis with WI38 cells was constantly expressed, they concluded that mitogenic signaling is not sufficient to modulate the Spry1 expression, and that Spry1, as appeared in earlier studies [19, 80, 81], is more likely modulated by differentiation processes.…”

Section: Sprouty: a Versatile Modulator With Complex Functionalitymentioning

confidence: 95%

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

Cited by 11 publications

References 25 publications

MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells

MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells

Sprouty2 but not Sprouty4 is a potent inhibitor of cell proliferation and migration of osteosarcoma cells

The developing story of Sprouty and cancer

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