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 - Funding Information:
M.W.B. and P.J.H. wrote the manuscript with input from J.P. M.W.B. and J.P. conducted literature reviews of the concepts outlined with input from P.J.H. This work is supported by funding from the National Institutes of Health (R01-CA120439). M.W.B. is a member of the National Institutes of Health Chemistry–Biology Interface Training Program (T32-GM070421). The authors declare the following competing financial interest(s): The University of Illinois has filed patents on some of the technology described in this manuscript.
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 -