Not all regions of a tumor are equal in terms of their oxygen levels. One clinically important implication of this is that tumors with large areas with low levels of oxygen (areas known as hypoxic regions) are associated with poor prognosis and treatment response.
A team of researchers, led by Bradly Wouters, at the University of Toronto, Canada, has determined that a cellular response pathway known as the unfolded protein response pathway helps protect human tumor cells from hypoxia and anticancer irradiation treatment.
Further analysis indicated that the unfolded response pathway increased expression of two proteins involved in a cellular process known as autophagy, which is known to act to protect cells in times of stress.
Importantly, inhibition of autophagy sensitized cultured human tumor cells to hypoxia and sensitized human tumors xenografted into mice to irradiation, leading the authors to suggest that targeting the molecules they identified as important might be of clinical benefit.
The research is reported in the Journal of Clinical Investigation.
- 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, and Bradly G. Wouters. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI40027
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