Washington University in St. Louis

Congratulations to Elise Alspach and the Stewart lab on their new publication!

Alspach, E, Flanagan, KC, Luo, X, Ruhland, MK, Huang, H, Pazolli, E, Donlin, MJ, Marsh, T, Piwnica-Worms, D, Monahan, J, Novack, DV, McAllister, SS, and Stewart, SA.  (2014)  p38MAPK plays a crucial role in stromal mediated tumorigenesis.  Cancer Discov.  March 26 [E-published ahead of print]

Abstract:  Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAFs) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood. Here we address a key unanswered question, how the SASP is sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus controls their stability. The importance of this regulatory mechanism is underscored by our findings that stromal-specific p38MAPK inhibition abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Our data suggest that targeting SASP mRNA stability through inhibition of p38MAPK will significantly aid the development of clinical strategies to target the TME.

To access this article, click here.

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