Identifier | HPI007390 |
Interaction | Apo2L/TRAIL <==> p53 |
Role & State | RS:0000074,inhibitor; |
Interaction Type | IT:0000076,inhibition; IT:0000346,ligand; |
Biological Process | BP:0006915,apoptosis; BP:0070265,necrosis; |
Biological Function | --- |
Subcelluar Location | --- |
Detection Method | --- |
Reference | 15604280_4, We show that irinotecan inhibits JAK2-STAT3/5-dependent expression of survival proteins (Bcl-x(L) and XIAP) and cooperates with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) to facilitate p53-independent apoptosis of colon cancer cells.
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Reference | 15604280_5, Whereas xenografts of p53-deficient colon cancer cells are relatively resistant to irinotecan compared with their p53-proficient counterparts, combined treatment with irinotecan and Apo2L/TRAIL eliminates hepatic metastases of both p53-proficient and p53-deficient cancer cells in vivo and significantly improves the survival of animals relative to treatment with either agent alone.
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Reference | 15604280_6, Although the synergy between chemotherapy and Apo2L/TRAIL has been ascribed to p53, our data demonstrate that irinotecan enhances Apo2L/TRAIL-induced apoptosis of tumor cells via a distinct p53-independent mechanism involving inhibition of JAK2-STAT3/5 signaling.
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Reference | 15604280_7, These findings identify a novel p53-independent channel of cross-talk between topoisomerase I inhibitors and Apo2L/TRAIL and suggest that the addition of Apo2L/TRAIL can improve the therapeutic index of irinotecan against both p53-proficient and p53-deficient colorectal cancers, including those that have metastasized to the liver.
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