PRL-3 dephosphorylates p38 MAPK to promote cell survival under stress
Yin Shi, Shengfeng Xu, Natalie Y.L. Ngoi, Qi Zeng, Zu Ye
Abstract
and hypoxia. Mechanistically, we proved that PRL-3 is a direct phosphatase of p38 MAPK under stressed conditions. Additionally, in mouse models of tumor metastasis, higher lung metastatic burden and lower p38 MAPK phosphorylation were found in mice seeded with GFP-PRL-3 expressing cells compared with those seeded with GFP-Ctrl cells. Taken together, our study identified a critical role of RPL-3 in tumorigenesis by negatively regulating p38 MAPK activity in order to facilitate tumor cell adaptation to a hypoxic stressed tumor microenvironment and suggests that PRL-3 could serve as a promising novel therapeutic target for cancer patients.
Topics & Concepts
BiologyMAPK/ERK pathwayPI3K/AKT/mTOR pathwayCancer researchCell biologyProtein kinase Bp38 mitogen-activated protein kinasesTumor microenvironmentApoptosisCarcinogenesisTumor progressionSignal transductionCancerGeneticsTumor cellsProtein Tyrosine PhosphatasesGenomics, phytochemicals, and oxidative stressEndoplasmic Reticulum Stress and Disease