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PERK/eIF2α signaling protects therapy resistant hypoxic cells through induction of glutathione synthesis and protection against ROS Kasper M. Rouschop, Ludwig J. Dubois, Tom G. Keulers, Twan van den Beucken, Philippe Lambin, Johan Bussink, Albert J. van der Kogel, Marianne Koritzinsky, and Bradly G. Wouters Abstract Hypoxia is a common feature of tumors and an important ... Read More

Translational control is a major contributor to hypoxia induced gene expression

Twan van den Beucken, Michael G. Magagnin, Barry Jutten, Renaud Seigneuric, Philippe Lambin, Marianne Koritzinsky and Bradly G. Wouters ,  28 June 2011  Abstract Background and purpose Hypoxia is a common feature of solid tumors that is associated with an aggressive phenotype, resistance to therapy and poor prognosis. Major contributors to these adverse effects are the transcriptional program activated by the HIF family of transcription factors as well as the translational response mediated ... Read More

AMPK regulates metabolism and survival in response to ionizing radiation

Vanessa E. Zannella, Dan Cojocari, Susan Hilgendorf, Ravi N. Vellanki, Stephen Chung, Bradly G. Wouters and Marianne Koritzinsky Volume 99, Issue 3 , Pages 293-299, June 2011   Abstract Background and purpose AMPK is a metabolic sensor and an upstream inhibitor of mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM dependent manner, but the cellular consequences of this phosphorylation event ... Read More

Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

Kasper M. A. Rouschop, Ludwig Dubois, Marco B. E. Schaaf, Twan van den Beucken, Natasja Lieuwes, Tom G. H. Keulers, Kim G. M. Savelkouls, Johan Bussink, Albert J. van der Kogel, Marianne Koritzinsky, Bradly G. Wouters Background and purpose: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting ... Read More

The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5

Kasper M.A. Rouschop, Twan van den Beucken, Ludwig Dubois, Hanneke Niessen, Johan Bussink, Kim Savelkouls, Tom Keulers, Hilda Mujcic, Willy Landuyt, Jan Willem Voncken, Philippe Lambin, Albert J. van der Kogel, Marianne Koritzinsky, Bradly G. Wouters Published in Volume 120, Issue 1 J Clin Invest. 2010;120(1):127–141     Tumor hypoxia is a common microenvironmental factor that adversely ... Read More

“Hypoxia signalling through mTOR and the unfolded protein response in cancer” Nature Rev. Cancer, 2008

Bradly G. Wouters & Marianne Koritzinsky  Abstract Hypoxia occurs in the majority of tumours, promoting angiogenesis, metastasis and resistance to therapy. Responses to hypoxia are orchestrated in part through activation of the hypoxia-inducible factor family of transcription factors (HIFs). Recently, two additional O2-sensitive signalling pathways have also been implicated: signalling through the mammalian target of rapamycin ... Read More