Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress.

ABSTRACT: It has been well established that the tumor microenvironment can promote tumor cell adaptation and survival. However, the mechanisms that influence malignant progression have not been clearly elucidated. We have previously demonstrated that cells cultured under hypoxic/anoxic conditions and transformed cells in hypoxic areas of tumors activate a translational control program known as the integrated stress response (ISR). Here, we show that tumors derived from K-Ras-transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a tumor microenvironment that favors the formation of functional microvessels. These observations were corroborated by a microarray analysis of polysome-bound RNA in aerobi

SUBMITTER: Blais JD 

PROVIDER: S-EPMC1698539 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature