Increased phosphorylation of eIF2α in chronic myeloid leukemia cells stimulates secretion of matrix modifying enzymes.

ABSTRACT: Recent studies underscore the role of the microenvironment in therapy resistance of chronic myeloid leukemia (CML) cells and leukemia progression. We previously showed that sustained mild activation of endoplasmic reticulum (ER) stress in CML cells supports their survival and resistance to chemotherapy. We now demonstrate, using dominant negative non-phosphorylable mutant of eukaryotic initiation factor 2 α subunit (eIF2α), that phosphorylation of eIF2α (eIF2α-P), which is a hallmark of ER stress in CML cells, substantially enhances their invasive potential and modifies their ability to secrete extracellular components, including the matrix-modifying enzymes cathepsins and matrix metalloproteinases. These changes are dependent on the induction of activating transcription factor-4 (ATF4) an

SUBMITTER: Podszywalow-Bartnicka P 

PROVIDER: S-EPMC5346746 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature