TY - JOUR
T1 - Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis
AU - Petersen, Sean L.
AU - Wang, Lai
AU - Yalcin-Chin, Asligul
AU - Li, Lin
AU - Peyton, Michael
AU - Minna, John
AU - Harran, Patrick
AU - Wang, Xiaodong
N1 - Funding Information:
This work is also supported by a program project grant from the National Cancer Institute (NCI) (PO1 CA 95471). J.D.M. is supported by grants (CA84971 and CA70907) from NCI. X.W. and P.H. are the cofounders of Joyant Pharmaceuticals, Inc.
PY - 2007/11/13
Y1 - 2007/11/13
N2 - A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs. Survey of a panel of 50 human non-small-cell lung cancer cell lines has revealed, surprisingly, that roughly one-quarter of these lines are sensitive to the treatment of Smac mimetic alone, suggesting that an apoptotic signal has been turned on in these cells and is held in check by IAP proteins. This signal has now been identified as the autocrine-secreted cytokine tumor necrosis factor alpha (TNFα). In response to autocrine TNFα signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.
AB - A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs. Survey of a panel of 50 human non-small-cell lung cancer cell lines has revealed, surprisingly, that roughly one-quarter of these lines are sensitive to the treatment of Smac mimetic alone, suggesting that an apoptotic signal has been turned on in these cells and is held in check by IAP proteins. This signal has now been identified as the autocrine-secreted cytokine tumor necrosis factor alpha (TNFα). In response to autocrine TNFα signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=35948994157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35948994157&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2007.08.029
DO - 10.1016/j.ccr.2007.08.029
M3 - Article
C2 - 17996648
AN - SCOPUS:35948994157
SN - 1535-6108
VL - 12
SP - 445
EP - 456
JO - Cancer Cell
JF - Cancer Cell
IS - 5
ER -