Metabolismo y cáncer - Encuentros en la Biología

Verano 2012
)*(+,#-'&.#/7/2862*"/
José Joaquín Serrano
Alumno de la Licenciatura en Biología de la Universidad de Málaga
[email protected]
!"#$%&'(#
!"# $%&'$%()*"# +%# ,-*%')."(,/-#%-#%0# (1-(%&# 2"# %'3"+4# 5"'"+"#+6&"-3%# 76(24#)%7$4# %-# 0"# +%3%((,/-# +%# "86%004'#.%-%' #
,7$0,("+4'#%-#0"#3&"-'94&7"(,/-#3674&,.:-,(";#<'#(,%&34#86%#%0#$%'4#+%#:'34'#%-#0"#"$"&,(,/-#+%# 0"' #(:060"'#("-(%&4'"'#%'31# 71'#
86%# (4-3&"'3"+4#=!"-%>#?@@AB>#$%&4#%-#04'#C0)74'#)%7$4'#'%# 2"-#2%(24#-67%&4'4'#"*"-(%'#%-#0"# (47$&%-',/-#+%# (/74#%0#
7%3"540,'74#+%# 0"' #(:060"'#("-(%&4'"'#0%'#$%&7,3%#7"-3%-%&#6-#9%-4)$4#7"0,.-4># 2"'3"#%0#$6-34#+%#00%."&#"# '%&#+%',.-"+4#&%D
(,%-3%7%-3%#(474#6-"#+%#0"'#-6%*"'#'%E"'#+%#,+%-)+"+#+%0#(1-(%&# =F"-"2"-#G#H%,-5%&.>#AI??B;#J4#%'3"74'#"-3%#"0.4#-6%*4#
(6"-+4#&%0"(,4-"74'#%0#7%3"540,'74#(4-#%0#(1-(%&K# %0#$,4-%&4#%-#"3&,56,&#"0#7%3"540,'74#6-#$"$%0#,7$4&3"-3%#%-#%0#$&4(%'4#
3674&"0#96%#%0#$&%7,4#J45%0#LM4#H"&56.>#86,%-#"001#$4&#04' #"E4'#AI#+%0#',.04#$"'"+4#45'%&*/#86%#0"'#(:060"'#3674&"0%' #$&%'%-D
3"5"-#6-"' #%0%*"+"'#3"'"' #+%#6)0,N"(,/-#+%# .06(4'"# +%# 7"-%&"# ,-+%$%-+,%-3%# "0#7%3"540,'74#4O,+")*4>#"#$%'"&#+%# 2"00"&'%#"#
6-"'#3%-',4-%'#+%#4OP.%-4#%0%*"+"'#=H"&56.>#?@AQB;# <0#"+*%-,7,%-34#+%# 0"' #-6%*"'#2%&&"7,%-3"'#+%#0"# 5,404.P"#740%(60"&#&%0%D
./#"#0"#5,486P7,("#(01',("#"# 6-#'%.6-+4#$0"-4>#G#0"#,-*%')."(,/-#51',("#%-#7%3"540,'74#86%+/#"0.4#%'3"-("+";#R%&4#2"# &%'6&.,D
+4#(4-#96%&N"#%-#04' #C0)74' #"E4' #%0# ,-3%&:'#$4&#%0#7%3"540,'74#3674&"0>#'45&%#34+4#.&"(,"'#"#"6-"&#96%&N"'#%-3&%# 0"'#-6%*"'#
3%(-404.P"'#G#0"'#7%34+404.P"'#51',("';#S,# 45T%)*4#%-#0"#$&%'%-3%# &%*,',/-# %'# $&%'%-3"&# "0.6-4'#+%# 04'#+%'(65&,7,%-34' #71'#
,7$4&3"-3%'#%-#%0#175,34#+%0#7%3"540,'74#%-#0"'#(:060"'#("-(%&4'"';
35
)*(+,#-'&.#/0-1234'2#/(1.#"+-
R4&#,7$4&3"-(,"#2,'3/&,(">#2"5&P"# 86%# (47%-N"&#2"50"-+4#+%#0"#$"&3%#71'#("&"(3%&P')("# ="#$&,4&,B#+%0#7%3"540,'74#3674&"0>#
%0# %9%(34#H"&56.;# U86P>#04'#"*"-(%'#71'#',.-,V(")*4'#*,%-%-#+%# 0"# %06(,+"(,/-#+%# 0"# ,+%-)+"+#+%# 04'#3&"-'$4&3"+4&%'#,7$0,("D
+4'#%-#0"#("$3"(,/-#+%#.06(4'"#G>#'45&%#34+4>#+%0#$"$%0#+%0#0"(3"34#%-#%0#(1-(%&>#"(36"-+4#(474#6-"#$4',50%# 740:(60"#'%E"0#86%#
$6%+"#+%'%-("+%-"&#$&4(%'4'#96-+"7%-3"0%'#(474#0"# "-.,4.:-%','>#0"#,-*"',*,+"+#3674&"0# =9"*4&%(,+"# $4&# %0#"75,%-3%# 1(,+4#
.%-%&"+4#$4&#%0#$&4$,4#0"(3"34B#4#0"#$&4$,"#&%.60"(,/-#+%0#7%3"540,'74#3674&"0#=F'6#G#W"5")-,>#AIIXB;
Y%-3&4#+%#0"#$&4$,"#&63"# .06(40P)("#$4+%74'#%-(4-3&"&#43&"'#$"&3%'#+%#0"# 7,'7"#"03%&"+";#<'#,-3%&%'"-3%#0"# %O,'3%-(,"#%-#0"#
(:060"#3674&"0#+%#6-"#,'4%-N,7"#+%#0"#$,&6*"34#(,-"'"#=RZB>#0"#RZDSA;#<'3"#,'494&7"#%' #7%-4'#"()*"#86%#0"#RZ#G#'6#%O$&%',/->#%-#
+%3&,7%-34#+%#0"#,'494&7"#[-4&7"0[>#$%&7,3%#86%# 04'#94'947%3"540,34' #"-3%&,4&%'#"0#94'94%-40$,&6*"34#=R<RB>#$6%+"-#"(6760"&D
'%#G#'%&#6)0,N"+4'#%-#0"#'P-3%','#+%#(47$6%'34'#-%(%'"&,4'#$"&"#7"-3%-%&#0"#$&40,9%&"(,/-#(%060"&>#(474#'4-#"7,-41(,+4'>#1(,+4'#
-6(0%,(4'#G#0P$,+4'#=S"N6&%\#!"#$%>#AII]>#Z&4%7%&#G#R46G''%.6&>#AIIXB;
!0%."+4'#"# %'3%# $6-34#%'#24&"#+%# 2"(%&# 7%-(,/-#"# 6-"#740:(60"# 86%#"+86,%&%#("+"#*%N#71'#,7$4&3"-(,"# %-#$&4(%'4'#&%0"D
(,4-"+4'#(4-#%0#(1-(%&;#<'3"#740:(60"#-4#%'#43&"#86%#%0#9"(34&#+%#3&"-'(&,$(,/-#F^_D?#=+%0#,-.0:'#&'()*+$#+,-./+0%!#1$/")234B;#F^_D
?#%'#6-#2%3%&4+P7%&4#(47$6%'34#$4&#6-"#'656-,+"+#5%3"#86%# '%# %O$&%'"# (4-')36)*"7%-3%# G#6-"#'656-,+"+#"09"#86%# '%#',-3%D
)N"#G#'%#+%.&"+"# %-#(4-+,(,4-%'#-4&7/O,("';# <'#%'3"#'656-,+"+#"09"#0"#86%# "+86,%&%#6-#$"$%0#&%0%*"-3%# %-#%0#(1-(%&;# U6-86%#
F^_D?#%'#96-+"7%-3"0#%-#%0#$&4(%'4#+%# 0"#"-.,4.:-%','>#(6"-+4#%0#3674&#'%#%-(6%-3&"#5"T4#(4-+,(,4-%'#+%#2,$4O,"#0"#&%.60"(,/-#
+%#'6#'P-3%','#G# %0,7,-"(,/-#$"&%(%#$&4*4("&# 3"75,:-#("75,4'#7%3"5/0,(4' #+%# ,7$4&3"-(,"# $"&"#0"#(:060"#3674&"0;# R"&"# '6#+%D
.&"+"(,/->#F^_D?#%'#7"&("+4#'%(6%-(,"07%-3%# $4&#0"#%-N,7"# $&40,0#2,+&4O,0"'"#G#6-"#65,86,)-"#0,."'"#=`F!>#9"(34&#+%#`4-#F,$$%0#
!,-+"6B#$"&"#'6#$4'3%&,4&#$&4(%'"7,%-34#$4&#%0#$&43%"'47"#AaW;#W,-#%75"&.4>#763"(,4-%'#%-#0"#0P-%"#.%&7,-"0#+%#+%3%&7,-"+"'#
%-N,7"'#+%0#(,(04#+%# 04'#1(,+4'#3&,("&54OP0,(4'#=bcUB># %-#(4-(&%34#0"'#%-N,7"'#'6((,-"34# +%'2,+&4.%-"'"# G#967"&"34#2,+&"3"'">#
*"-#"# $&474*%&#0"# "(6760"(,/-#+%#04'#7%3"540,34'#'6((,-"34#4#967"&"34>#04'#(6"0%'#,-2,5%-#(47$%))*"7%-3%# #0"#$&40,0#2,+&4O,D
0"'"# %-("&."+"#+%# &%.60"&#0"#+%.&"+"(,/-#+%# F^_D?"09"># 04#86%# $%&7,3%# 86%# %'3"# 740:(60"# $6%+"# +,7%&,N"&#(4-#F^_D?5%3"# =d4D
M0,%5#G#b470,-'4-># AII]B;# !"#("&3"# +%#0,5%&3"+# #$"&"# 0"# "(36"(,/-#+%# F^_D?#*"# "# $%&7,)&#86%#%'3%# 9"(34&#+%# 3&"-'(&,$(,/-#3&"-'D
"()*%# "#0"# $,&6*"34#+%'2,+&4.%-"'"# \,-"'"# ?>#6-"# %-N,7"# 86%# 94'94&,0"# "# 0"#$,&6*"34#+%'2,+&4.%-"'"#G#0"# ,-"()*"># ,7$,+,%-+4#
86%# '%#.%-%&%#"(%)0Dc4U>#+%#94&7"# 86%# :'3%# -4#$6%+%# %-3&"&#%-#%0#bcU#G#.%-%&"&#%86,*"0%-3%' #&%+6(34&%'>#(47$&47%)%-+4#0"#
94'94&,0"(,/-#4O,+")*"#=Z&4%7%&#"-+#R46G''%.6&>#AIIXB;
)*(+,#-'&.#/-'$34'2#/(1.#"+-
<-#0"'#(:060"' #3674&"0%'#3"75,:-#'%#%-(6%-3&"-#'45&%%O$&%'"+"'#%-N,7"'#(0"*%# +%0#7%3"540,'74#0,$P+,(4>#(474#%'#0"# 1(,+4#
.&"'4#',-3"'"# =_UWB;# !"# '45&%%O$&%',/-#+%# %'3"# %-N,7"# $%&7,3%# 7"-3%-%&# 6-"#%0%*"+"# *%04(,+"+#+%# 'P-3%','#+%# 1(,+4'#.&"'4'>#
%'%-(,"0%'# $"&"# 0"# 94&7"(,/-# +%# 7%75&"-"'# $0"'71)("'># '6'3%-3"-+4#+%# %'3"# 94&7"# 0"# $&40,9%&"(,/-# 3674&"0# =H"-.# !"# $%>#
AII]B;#<'3"#'P-3%','#+%# 1(,+4'#.&"'4' #%'#3"75,:-#+%$%-+,%-3%#+%# 0"# +,'$4-,5,0,+"+#+%# $4+%&#&%+6(34&#%-#94&7"#+%# JUYRF>#(6G4#
4&,.%-#'%#2"00"#%-#0"#9"'%#4O,+")*"#+%#0"#&63"#+%#0"'#$%-34'"'#94'9"34#=RRRB>#%'3"50%(,:-+4'%#6-"#&%0"(,/-#%-3&%# 0"#RZDSA#G#0"#_UW#
%-#%0# 7%3"540,'74#3674&"0#=Z&4%7%&# G#R46G''%.6&# AIIX># S%-%-+%N#G#!6$6#AIIeB;# <'3"# .%-%&"(,/-#+%# JUYRF#3"75,:-#'%#*%#
9"*4&%(,+"# $4&# 0"# ,-2,5,(,/-#+%# 0"# %O$&%',/-#+%# 6-#74+60"+4&#+%0#7%3"540,'74#86%# '%# %-(6%-3&"# &%.60"+4#$4&#%0#$&4+6(34#+%0#
.%-#bR]f;#<'3%#74+60"+4&#%'#b^dUg#=+%0#,-.0:'>#56783+,-./!-#9%'/)%':+:#$,-#$()("):+:#2!9.%$")2B>#86%#%-#(4-+,(,4-%'#-4&7"0%'#
"G6+"#"# 7"-3%-%&#04'#-,*%0%'#+%# &"+,("0%'#0,5&%'#+%#4OP.%-4#=gLWB#5"T4'#G#"#"67%-3"&#04'#-,*%0%'#+%#JUYRF>#&%+6(,%-+4#%0#h6T4#
.06(40P)(4;#<-#%0#(1-(%&#0"# %O$&%',/-#+%#b^dUg#%'31#,-2,5,+";#<'34#$6+,%&"#$"&%(%&#(4-3&"D,-36,)*4#%-#6-#$&,7%&#747%-34>#$%&4#
+6&"-3%#%0#$&4(%'4#3674&"0#'%#$&4+6(%# 6-#"67%-34#+%# 0"#.06(40,','>#$4&#04#86%#'6#,-2,5,(,/-#%'#96-+"7%-3"0;#U+%71'>#0"#%O$&%D
',/-#+%#RZDSA#"G6+"#"#86%#+,(24#"67%-34#+%#0"#.06(40,','#$%&7,3"#86%#'%# +%&,*%-#$"&3%#+%#04'#7%3"540,34'#"#0"#&63"#+%# 0"' #$%-D
34'"'#94'9"34#=RRRB#G#"'P#.%-%&"&#JUYRF#%-#.&"-+%'#("-)+"+%'#(4-#%0#45T%34#+%#7"-3%-%&#0"#$&40,9%&"(,/-#(%060"&# =i46-.#G#U-D
+%&'4-#AIIXB;
5162'%6/.'(#2#64"'+-/7/2862*"
!"# 7,34(4-+&,"># (474# .%-%&"+4&# 96-+"7%-3"0# +%# %-%&.P"# (%060"&># 3"75,:-#)%-%# 6-# $"$%0# (&P)(4#%-# %0#$&4.&%'4#2"(,"# %0#
("75,4#7%3"5/0,(4>#'45&%# 34+4#+%5,+4#"# 0"# .%-%&"(,/-#+%# gLW# (474#(4-'%(6%-(,"# +%# 6-#%0%*"+4#7%3"540,'74#4O,+")*4#86%#
%O(%+%# 0"# ("$"(,+"+#+%# 0"# ("+%-"# +%#3&"-'$4&3%# %0%(3&/-,(4#7,34(4-+&,"0#=<bcB;#!"# (%&("-P"#%-3&%#0"#<bc#G#%0#YJU#7,34(4-+&,"0#
2"(%#86%#0"#$&4+6((,/-#+%# gLW>#86%#'4-#".%-3%'#3/O,(4'#$"&"#%0#YJU>#$6%+"#$&4*4("&#763"(,4-%'>#86%#3&6-86%-#0"#<bc#G#.%-%D
Vol.5 ¦ Nº 138-139
&%-#71'#gLW#86%# $&4*486%-#71'#763"(,4-%'>#%-3&"-+4#%-#6-#(,(04#+%#&%3&4"0,7%-3"(,/-#$4',)*"# 86%#$6%+%# 9"*4&%(%&#%0#$&4D
(%'4#3674&"0#=b&"(244327"-#!"#$%;#AII@B;#
<0#7%3"540,'74#3674&"0#3"75,:-#74+,V("#43&"'#'%E"'#+%# ,+%-)+"+#+%0#(1-(%&K#%'3%#%'#%0#("'4#+%# 0"#%*"',/-#+%#0"#"$4$34','#
7%+,"+"#$4&#0"#"'4(,"(,/-#"#-,*%0#+%# 0"#7%75&"-"# 7,34(4-+&,"0#%O3%&-"#+%# 0"# 2%O486,-"'"# =FZB#G#+%#6-#("-"0#"-,/-,(4#+%$%-D
+,%-3%#+%#*403"T%#=`YUcB#=R%+%&'%->#AIIeBK#%'3"#"'4(,"(,/-#%'31#$&474*,+"#$4&#U\3>#6-"#\,-"'"# 86%#9"*4&%(%#0"#'6$%&*,*%-(,"#G#
%0# (&%(,7,%-34# (%060"&>#"# 3&"*:'#+%# '6# ,-3%&"((,/-# +%# 43&"'# +4'# %-N,7"'#(0"*%'#%-#0"# &%.60"(,/-# +%0# 7%3"540,'74># 6-"# ',36"+"#
<.(:"2!$=>#+%# U\3>#0"#R^fZ># G# 43&"# ',36"+"# <-)?,:"2!$=>># 0"# 7bLg#=Z&4%7%&# G#R4G''%.6&># AIIXB;# U\3# $6%+%# &%'603"&# "()*"+"#
(474#(4-'%(6%-(,"# +%#0"# ,-2,5,(,/-#+%# 0"# 94'9"3"'"# Rb<J># 0"# (6"0# "(3C"#(474#6-#&%.60"+4&#-%.")*4#+%# U\3;#!"# ,-"()*"(,/-#+%#
Rb<J#%'#00%*"+"#"#("54#96-+"7%-3"07%-3%# $4&#gLW;#W%#$6%+%#%'3"50%(%&#"86P#6-"#(4-%O,/-#%-3&%# Rb<J#G#b^dUg>#+%#94&7"# 86%#
0"#+%'&%.60"(,/-#+%#b^dUg#(47$&47%3%#0"#%O$&%',/-#+%#Rb<J#+%#94&7"#,-+,&%(3">#"#3&"*:'#+%#0"#$&4+6((,/-#+%#gLW#$4&#0"#<bc;
5-19#&/.*(+,%-'2#&
!4' #3674&%'#'%# (47$4&3"-# (474#/&."-4'># %-#0"# 7%+,+"# %-#86%# $6%+%-#%'3"50%(%&#h6T4'#(4-#43&"'#$"&3%'#+%0# (6%&$4#+%0#
24'$%+"+4&>#3"-34#"#-,*%0#(%060"&>#%-3&%#0"'#(:060"' #3674&"0%'#G#0"'#(:060"'#%'3&471)("'># 6)0,N"-+4#%'3"'#C0)7"'#%0#0"(3"34#$"&"#
&%.%-%&"&#$,&6*"34>#86%#*6%0*%#"#0"#(:060"' #("-(%&4'"#$"&"#'%&#6)0,N"+4#%-#0"#'P-3%','#+%#UbR#$4&#94'94&,0"(,/-#4O,+")*"#=Z46\46D
&"\,'#!"#$%@#AIIaB>#(474#"#-,*%0# +%#/&."-4'># +%# 94&7"# 86%#'%# %'3"50%(%# 6-"#%'$%(,%#+%#(,(04#+%# c4&,#%-3&%# %0#24'$%+"+4&#G#%0#
3674&>#%-*,"-+4#:'3%# 0"(3"34#2"(P"#%0#2P."+4>#86%#04#(4-*,%&3%# %-#.06(4'"# 86%# %'#("$3"+"#+%#-6%*4#$4&# %0# 3674&>#$%&7,)%-+4#
6-#&%(,(0"+4#+%0#0"(3"34#.%-%&"+4#%-#%O(%'4#$4&# 0"# (:060"# 3674&"0K# %'3%# &%(,(0"+4#'6$4-%>#-4#45'3"-3%>#6-#%0%*"+4#(4'3%# %-%&D
.:)(4#=b,'+"0%#AIIAB;
)*(+,#-'&.#/(1.#"+-/7/*$'0*6:('2+
F"'3"# "24&"# '%# 2"# 2%(24#%*,+%-3%# 0"# &%0"(,/-#%-3&%#7%3"540,'74#G#.%-:)("# 3674&"0%';# <'3"# &%0"(,/-#'%# %O)%-+%#2"'3"# %0#
-,*%0#%$,.%-:)(4>#+4-+%#$4+%74'#%-(4-3&"&#("75,4'#%-#+%3%&7,-"+4' #&%',+64'#+%#0,',-"#+%# 0"'#2,'34-"'#$4&#"(%)0"(,/->#0"#(6"0#
$"&%(%# %'3"&#$&474*,+"# $4&#%0#%O(%'4#+%#"(%)0Dc4U#86%#'%#.%-%&"#+%# 0"#%0%*"+"#"()*,+"+#+%#UbR#(,3&"34#0,"'"#=Uc!B;# <'3"#"(%)D
0"(,/-#$6%+%# &%*%&)&'%# .&"(,"'#"#0"# "((,/-#+%# +%'"(%)0"'"'#+%$%-+,%-3%'#+%# JUY>#0"'#',&36,-"'#=F",.,'#G# W,-(0",&# AI?IB;# <'#6-#
("7$4#86%# -%(%',3"# 71' #3&"5"T4># $%&4#'%# 2"# +%74'3&"+4#86%#0"#'6$&%',/-#7%+,"+"#$4&#gJU,#+%# 0"# Uc!# #,-2,5%# %0#(&%(,7,%-34#
+%0#3674&#=F"3N,*"'',0,46#!"#$%;>AII]B;
36
;*&(#<'='2+2'%6
b"75,:-#$4+%74'#%-(4-3&"&#86%#(474#(4-'%(6%-(,"#+%#'6#"()*,+"+#7%3"5/0,("#+%'4&5,3"+">#0"'#(:060"'#3674&"0%'#.%-%&"-#
6-"# .&"-#("-)+"+#+%#$&4+6(34'#3/O,(4'#$"&"#'P#7,'7"';#W%#$,%-'"#86%#0"'#(:060"'#3674&"0%'#$4+&P"-#&%86%&,&#+%# 7%("-,'74'#+%#
+%34O,V("(,/-#$"&"#'45&%*,*,&;#<'%# '%&P"#%0#("'4#+%#0"#%-N,7"#JjY^k>#6-"# 2,+&40"'"#86%#"(3C"#'45&%# %0#$440#+%#-6(0%/)+4'#%0,7,D
-"-+4#"86%004'#86%#-4#'4-#-6(0%/',+4'#3&,94'9"34#("&"(3%&P')(4'#+%0#YJU#=F'6#G#W"5")-,>#AIIXB;#S1'#%'96%&N4#'%#+%5%#$4-%&#%-#
+,06(,+"&#0"#,7$0,("(,/-#+%#%'3%#)$4#+%#%-N,7"'#%-#%0#+%'"&&4004#3674&"0;
>/-+/*&$*"+/4*/6#?*4+4*&
<'3"#%'#'404#6-"#$%86%E"# 76%'3&"#+%#0"#760)36+#+%#$&4(%'4'#&%0"(,4-"+4'#(4-#%0#7%3"540,'74#86%# 9"*4&%(%-#%0#+%'"&&4004#
+%0# 3674&;# F'6#G#W"5")-,># %-#'6#%-'"G4# +%# AIIX#%-#A!%%>#$0"-3%"-#6-"# '%&,%# +%# (6%')4-%'#"(%&("#+%0#7%3"540,'74#3674&"0>#
(474#(61-#7"0%"50%#%'#%0#7%3"540,'74#+%0#(1-(%&>#',# '4-#-%(%'"&,4'#34+4'#04'#%'3"+4'#+%#"+"$3"(,/-#7%3"5/0,("#$"&"# 86%# 0"#
(:060"# 3674&"0# $&4.&%'%# +%'+%# 0"# %3"$"# +%# 3674&#$&,7"&,4# 2"(,"# 0"# ,-*"',/-#G# 0"# 7%31'3"','#4#',# 0"# (:060"# 3674&"0#$4'%%# &63"'#
7%3"5/0,("'#C-,("'>#86%# -4#%'31-#$&%'%-3%'#%-#0"'#(:060"'#-4&7"0%';#<'3"'#G#43&"'#$&%.6-3"'#'4-#%0#-6%*4#$6-34#+%# $"&)+"#%-#0"#
06(2"#$4&#(47$&%-+%&#%0#7%3"540,'74#3674&"0;
Bibliografía citada:
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Gottlieb E, Tomlinson IP (2005). Mitochondrial tumor supressors: a genetic and biochemical update. Nature reviews cancer 5: 857-866.
Haigis MC, Sinclair DA (2010). Mammalian sirtuins: biological insights and disease relevance. Annual Review Pathology 5: 253-295.
Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell 144: 646-674
Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB (2005). ATP citrate lyase
inhibition can suppress tumor cell growth. Cancer cell 8: 311-321.
Hsu P, Sabatini D (2008). Cancer cell metabolism: Warbug and Beyond. Cell 134: 703-708
Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E (2006). Comparison of metabolic pathways between cancer cells and stromal cells in
colorectal carcinomas: a metabolic survival role for tumor associated stroma. Cancer research 66: 632-637.
Kroemer G, Pouyssegur J (2008). Tumor cell metabolism: Cancer´s achilles heel. Cancer cell 13: 472-482
Lane D (1992). p53, the guardian of genome. Nature 358: 6-15.
Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005). Pyruvate Kinase type M2 and its role in tumor growth and spreading. Seminars cancer
biology 15: 300-308.
Menendez JA, Lupu R (2007). Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature Reviews Cancer 7: 763-777.
Pedersen PL (2007). Warbug, me and Hexokinase 2: Multiple discoveries of key molecular events underliying one of cancer´s most common
phenotypes the “Warbug effect”. Journal Bioenergetics Biomembranes 39: 211-222.
Tisdale MJ (2002). Cachexia in cancer patients. Nature Reviews Cancer 2 862-871.
Trachooman D, Alexandre J, Huang P (2009). Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature
Reviews Drug Discovery 8: 579-591.
Wang HQ, Altomare DA, Skele KL, Poulikakos PI, Kuhajda FP, Di Cristofano A, Testa JR (2005). Positive feedback regulation between AKT
activation and fatty acid synthase expression in ovarían carcinoma cells. Oncogene 24: 3574-3582.
Warbug O, Posener K, Negelein E (1924). Über den Stoffweschsel der tumoren. Biochemie Zentrum 152, 319-344.
Young CD, Anderson SM (2008). Sugar and fat - that’s where it’s at: metabolic changes in tumors. Breast Cancer Research 10: 202-211.
Vol.5 ¦ Nº 138-139