Cross‐talk between sphingosine‐1‐phosphate and <scp>EGFR</scp> signaling pathways enhances human glioblastoma cell invasiveness

Cattaneo, Maria Grazia; Vanetti, Claudia; Samarani, Maura; Aureli, Massimo; Bassi, Rosaria; Sonnino, Sandro; Giussani, Paola

doi:10.1002/1873-3468.13000

Cited by 18 publications

(27 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a later study, our data indicated reduced levels of S1P in platelet-rich plasma of GBM patients ( c ) [56]. These observations point towards a key role of S1P signaling system in the pathophysiology of GBM and are in agreement with studies from other groups [87,88]. Data are adapted from Bien-Möller et al [75] and Marx et al [56] and are shown as box plots representing the median as horizontal bars as well as the 5th and 95th percentile.…”

Section: Figuresupporting

confidence: 89%

The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma

Marx

Xiao

Baschin

et al. 2019

Cancers

View full text Add to dashboard Cite

The link between thrombocytosis and malignancy has been well known for many years and its associations with worse outcomes have been reported mainly for solid tumors. Besides measuring platelet count, it has become popular to assess platelet function in the context of malignant diseases during the last decade. Malignant gliomas differ tremendously from malignancies outside the central nervous system because they virtually never form distant metastases. This review summarizes the current understanding of the platelet–immune cell communication and its potential role in glioma resistance and progression. Particularly, we focus on platelet-derived proinflammatory modulators, such as sphingosine-1-phosphate (S1P). The multifaceted interaction with immune cells puts the platelet into an interesting perspective regarding the recent advances in immunotherapeutic approaches in malignant glioma.

show abstract

Section: Figuresupporting

confidence: 89%

The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma

Marx

Xiao

Baschin

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…S8), indicating that the role of S1P in extrusion may be linked to its crosstalk with EGFR-ERK signaling. Indeed, ERK can stimulate production of S1P by activating Sphingosine Kinases 30,31 and S1P stimulates EGFR activation during development and in glioblastomas 32,33 . Taken together these data demonstrate that either ERK or p38 MAPK signaling dynamics can initiate ADAM17-EGFR paracrine signaling to promote extrusion of unfit cells from monolayers, therefore coordinating epithelial homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Collective MAPK Signaling Dynamics Coordinates Epithelial Homeostasis

Aikin

Peterson

Pokrass

et al. 2019

Preprint

View full text Add to dashboard Cite

12Epithelial tissues are constantly challenged by individual cell fate decisions while 13 maintaining barrier function. During oncogenesis, mutant and normal cells also differ in their 14 signaling states and cellular behaviors creating competitive interactions that are poorly 15 understood. Here we show that the temporal patterns of MAPK activity are decoded by the 16 ADAM17-EGFR paracrine signaling axis to coordinate migration of neighboring cells and promote 17 extrusion of aberrantly-signaling cells. Concurrently, neighboring cells increase proliferation to 18 maintain cell density while oncogene expressing cells undergo cell cycle arrest. Moreover, the 19 stress MAPK p38 elicits the same paracrine signaling and extrusion response, suggesting that 20 the ADAM17-EGFR pathway constitutes a quality control mechanism to eliminate and replace 21 unfit cells from epithelial tissues. Overall, we show that the temporal patterns of MAPK activity 22 coordinates both single and collective cell behaviors to maintain tissue homeostasis. 23 24 27 cancers 1 . In normal conditions the ERK pathway promotes proliferation, differentiation, survival 28 and cell migration 2 . Conversely, during oncogenesis mutations or amplification of ERK pathway 29 components can also promote oncogene-induced senescence 3 (OIS) or cellular extrusion from 30 epithelial monolayers 4,5 . The mechanisms underlying dose dependent effects of ERK signaling 31 have been intensely studied using bulk cell population assays. However, the advent of single cell 32 analysis has shown that single cells often behave qualitatively different than bulk populations. In 33 fact, in vivo and in vitro studies have now shown that pulsatile or sustained ERK activity have 34 different effects on cell fate 6-12 . Whether oncogenic perturbations also have different functional 35 outcomes depending on downstream signaling dynamics remains unknown. To address this 36 question, an isogenic single-cell approach with temporal control of oncogene expression is 37 needed. 38 39 Recent in vivo studies revealed that oncogene expression can trigger cell-cell competition and 40 tissue level responses involving normal neighboring cells 13-16 . During these events, the 41 mechanistic basis of competition and the signaling events involved in recognition between normal 42 and diseased cells are poorly understood. Coincidentally, propagating ERK signaling waves that 43 depend on the sheddase ADAM17 have been observed in mouse epidermis and intestinal 44 organoids, but the physiological role of these collective signaling events in homeostasis remains 45 unclear 7,8,17 . Understanding of the context-dependent mechanisms of paracrine signaling and cell-46 cell competition upon oncogene expression holds the key to unlocking new therapeutic strategies. 47 48 Here we combine live cell imaging of signaling biosensors with inducible expression of oncogenes 49 to study the cell autonomous and non-cell autonomous effects of oncogene expression in 50 epithelial monolayers. Our data shows that pulsa...

show abstract

“…It is now known that S1P metabolism is tightly regulated. In particular, new pieces of evidence indicating specific roles for SK1 and SK2 in different diseases, including cancer, cardiovascular system and central nervous system (CNS) affections, inflammation, and diabetes, have been recently published (Pyne et al, 2016; Cattaneo et al, 2018). In particular, the role of S1P/SK2 pathway in regulating the survival of the dopaminergic neurons has emerged, suggesting that dysregulation of this pathway might be relevant to the clinical development of Parkinson’s disease (PD); in addition, a role for SK1 and SK2 has also been suggested in the onset of AD (Pyne et al, 2016).…”

Section: Sphingosine 1-phosphate Metabolism and Signalingmentioning

confidence: 99%

Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases

et al. 2019

Self Cite

View full text Add to dashboard Cite

The central nervous system is characterized by a high content of sphingolipids and by a high diversity in terms of different structures. Stage- and cell-specific sphingolipid metabolism and expression are crucial for brain development and maintenance toward adult age. On the other hand, deep dysregulation of sphingolipid metabolism, leading to altered sphingolipid pattern, is associated with the majority of neurological and neurodegenerative diseases, even those totally lacking a common etiological background. Thus, sphingolipid metabolism has always been regarded as a promising pharmacological target for the treatment of brain disorders. However, any therapeutic hypothesis applied to complex amphipathic sphingolipids, components of cellular membranes, has so far failed probably because of the high regional complexity and specificity of the different biological roles of these structures. Simpler sphingosine-based lipids, including ceramide and sphingosine 1-phosphate, are important regulators of brain homeostasis, and, thanks to the relative simplicity of their metabolic network, they seem a feasible druggable target for the treatment of brain diseases. The enzymes involved in the control of the levels of bioactive sphingoids, as well as the receptors engaged by these molecules, have increasingly allured pharmacologists and clinicians, and eventually fingolimod, a functional antagonist of sphingosine 1-phosphate receptors with immunomodulatory properties, was approved for the therapy of relapsing–remitting multiple sclerosis. Considering the importance of neuroinflammation in many other brain diseases, we would expect an extension of the use of such analogs for the treatment of other ailments in the future. Nevertheless, many aspects other than neuroinflammation are regulated by bioactive sphingoids in healthy brain and dysregulated in brain disease. In this review, we are addressing the multifaceted possibility to address the metabolism and biology of bioactive sphingosine 1-phosphate as novel targets for the development of therapeutic paradigms and the discovery of new drugs.

show abstract

Cross‐talk between sphingosine‐1‐phosphate and EGFR signaling pathways enhances human glioblastoma cell invasiveness

Cited by 18 publications

References 57 publications

The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma

The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma

Collective MAPK Signaling Dynamics Coordinates Epithelial Homeostasis

Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases

Contact Info

Product

Resources

About