Oncotarget

Reviews:

The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells

Isabelle Corre, François Paris and Jacques Huot _

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Oncotarget. 2017; 8:55684-55714. https://doi.org/10.18632/oncotarget.18264

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Abstract

Isabelle Corre1,*, François Paris1,* and Jacques Huot2

1CRCINA, INSERM, CNRS, Université de Nantes, Nantes, France

2Le Centre de Recherche du CHU de Québec-Université Laval et le Centre de Recherche sur le Cancer de l’Université Laval, Québec, Canada

*Co-first authors

Correspondence to:

Jacques Huot, email: [email protected]

Keywords: p38MAPK, endothelial cells, oxidative stress, cancer, endothelial dysfunction

Received: March 29, 2017    Accepted: May 03, 2017    Published: May 29, 2017

ABSTRACT

By gating the traffic of molecules and cells across the vessel wall, endothelial cells play a central role in regulating cardiovascular functions and systemic homeostasis and in modulating pathophysiological processes such as inflammation and immunity. Accordingly, the loss of endothelial cell integrity is associated with pathological disorders that include atherosclerosis and cancer. The p38 mitogen-activated protein kinase (MAPK) cascades are major signaling pathways that regulate several functions of endothelial cells in response to exogenous and endogenous stimuli including growth factors, stress and cytokines. The p38 MAPK family contains four isoforms p38α, p38β, p38γ and p38δ that are encoded by four different genes. They are all widely expressed although to different levels in almost all human tissues. p38α/MAPK14, that is ubiquitously expressed is the prototype member of the family and is referred here as p38. It regulates the production of inflammatory mediators, and controls cell proliferation, differentiation, migration and survival. Its activation in endothelial cells leads to actin remodeling, angiogenesis, DNA damage response and thereby has major impact on cardiovascular homeostasis, and on cancer progression. In this manuscript, we review the biology of p38 in regulating endothelial functions especially in response to oxidative stress and during the metastatic process.


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