2016
DOI: 10.18632/oncotarget.9206
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Hypoxia regulates TRAIL sensitivity of colorectal cancer cells through mitochondrial autophagy

Abstract: The capacity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to selectively induce cell death in malignant cells triggered numerous attempts for therapeutic exploitation. In clinical trials, however, TRAIL did not live up to the expectations, as tumors exhibit high rates of TRAIL resistance in vivo. Response to anti-cancer therapy is determined not only by cancer cell intrinsic factors (e.g. oncogenic mutations), but also modulated by extrinsic factors such as the hypoxic tumor microenvironm… Show more

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Cited by 22 publications
(24 citation statements)
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“…This difference could be explained by either a lower penetration rate of LUV-TRAIL in this area or a lower efficiency of the drug in a low-oxygen environment. Higher resistance to TRAIL in hypoxic microenvironments has indeed been previously described 47 .…”
Section: Resultssupporting
confidence: 62%
“…This difference could be explained by either a lower penetration rate of LUV-TRAIL in this area or a lower efficiency of the drug in a low-oxygen environment. Higher resistance to TRAIL in hypoxic microenvironments has indeed been previously described 47 .…”
Section: Resultssupporting
confidence: 62%
“…However, loss or mutation of the death receptors targeted by TRAIL may lead to drug resistance ( 27 ). Therefore, it is important to determine the molecular mechanisms underlying TRAIL-induced apoptosis in order to develop novel therapeutic agents that circumvent resistance ( 28 , 29 ).…”
Section: Discussionmentioning
confidence: 99%
“…HIF-1 alpha can activate genes and their translated proteins, such as erythropoietin [8], glucose transporters [9], and vascular endothelial growth factor (VEGF) [10]. The change for HIF-1 alpha has been detected in colorectal cancer (CRC) [11, 12] and several authors have described its importance in angiogenesis and CRC growth [13, 14]. Ki67, a nuclear protein, affects cellular proliferation and it reflects a reversible change in cellular bioactivity during neoplastic progression [15].…”
Section: Introductionmentioning
confidence: 99%