TY - JOUR
T1 - Procaspase-3 Overexpression in Cancer
T2 - A Paradoxical Observation with Therapeutic Potential
AU - Boudreau, Matthew W.
AU - Peh, Jessie
AU - Hergenrother, Paul J.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
AB - Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
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U2 - 10.1021/acschembio.9b00338
DO - 10.1021/acschembio.9b00338
M3 - Review article
C2 - 31260254
AN - SCOPUS:85071522613
SN - 1554-8929
VL - 14
SP - 2335
EP - 2348
JO - ACS chemical biology
JF - ACS chemical biology
IS - 11
ER -