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

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

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

Jaime D Blais,Christina L Addison,Robert Edge,Theresa Falls,Huijun Zhao,Kishore Wary,Costas Koumenis,Heather P Harding,David Ron,Martin Holcik,John C Bell,

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 aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs. This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken with the concomitant Perk-dependent translational induction of additional proangiogenic genes identified by our microarray analysis, this study suggests that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating the translation of angiogenic factors necessary for the development of functional microvessels and further supports the contention that the Perk pathway could be an attractive target for novel antitumor modalities.

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

JD Blais,CL Addison,R Edge,T Falls,H Zhao,K Wary,C Koumenis,HP Harding,D Ron,M Holcik,JC Bell,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: eif-2 kinase research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: eif-2 kinase research

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 26

Page Numbers: 9517-32

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 9

MONTH: 10

YEAR: 2006

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 8109087

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

KEYWORDS: eIF-2 Kinase

MESH TERMS: physiology

Chemical & Substance for Abstract: Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress. Information

Substance Name: PERK kinase

Registry Number: EC 2.7.10.-

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

AFFILIATION: Ottawa Health Research Institute, Ottawa, ON K1H 1C4, Canada.

Country: United States

AGENCY: United States NHLBI

GRANT: HL079356

ACRONYM: HL

MEDLINETA: Mol Cell Biol

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