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Figure 2 | Clinical and Translational Medicine

Figure 2

From: Contribution of uric acid to cancer risk, recurrence, and mortality

Figure 2

Elevated UA and reduced intracellular XOR contribute to tumor cell proliferation, migration, and survival. ROS scavenging properties of extracellular UA are postulated to promote cancer cell growth and survival in part by protecting cells from oxidative stress induced apoptosis. This arises because tumor cells in general exhibit poor capacity to survive oxidative stress compared with normal cells and may therefore be protected by the antioxidant ROS scavenging properties of UA (J-Shaped dose–response curve;[32]). Loss of XOR expression in the most aggressive cancer cells also contributes to tumor cell proliferation, migration, and survival. In cells showing high level XOR expression, XOR modulates COX-2 and MMP expression reducing migratory activity[136]. However, loss of XOR expression in cancer cells increases COX-2 levels, MMP expression, and migratory activity. Loss of XOR expression may arise for many reasons, including the entry of UA into cancer cells. Import of UA into XOR deficient cancer cells may further promote proliferation and survival in part by stimulating expression of COX-2. The diminished XOR expression found in aggressive cancer cells would result in shunting the XOR substrates hypoxanthine and xanthine into the salvage pathway, providing substrates for nucleotide synthesis, tumor growth, and proliferation. The independent effects of leptin on cancer cells notwithstanding[85, 113], the elevated levels of leptin observed in MetS associated cancer may also drive these processes both by inducing hyperuricemia and by down regulating cancer cell XOR.

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