7/23/2019 Enam Perubahan Mendasar Dalam Fisiologi Sel Yang Menentukan Fenotipe Ganas

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ENAM PERUBAHAN MENDASAR DALAM FISIOLOGI SEL YANG MENENTUKAN FENOTIPE

GANAS

1. Self-suciec! "#e$%&sil'& se(i)i* si!&l +e),u#u%&- Ge !&$ #ei$'&,'& +e),u#u%& ,# +&(& sel '&'e)/ '$e- Mu,&si (&)i +),$e "$e +e()$ +e),u#u%&*

- M&#+u #e()$ +e),u#u%& sel 0&l&u+u ,i(&' ,e)(&+&, si!&l

+e()$ +e),u#u%& !&$ )#&l.- P)(u'!& (iseu, '+),ei !&$ ,i(&' #e#ili'i ele#e )e$ul&,)i' (&

+)(u'si!& ,i(&' e)$&,u$ +&(& f&c,) +e),u#u%& &,&u si!&l e's,e)&l

l&i!&

• 2i)i +)life)&si )#&l/

- Te)i'&,!& su&,u f&c,) +e),u#u%& 'e )ese+,) s+esi3'!& (i #e#)&e

sel

- A',i4&si )ese+,) f&c,) +e),u#u%& sec&)& ,)&sie (& ,e)&,&s !&$'e#u(i& #e$&',if'& ee)&+& +),ei ,)&s(u'si-si!&' (i le&) (&l&#

#e#)&e +l&s#&- T)&s#isi si!&l (i,&s(u'si #eli,&si si,sl #eu5u i,i sel #el&lui

+e)&,&s& 'e (u&- I(u'si (& &',i4i,&s f&c,) )e$ul&,)i' i,i sel !&$ #e#icu ,)&s')i+si DNA- Sel #&su' 'e (&l&# (& #e$i'ui si'lus sel !&$ &'%i)!& #e!e&'& sel

#e#el&%

• F&c,) +e),u#u%&- Sel '&'e) #e#+e)le% 'e#&#+u& u,u' ,u#u% se(i)i '&)e& #&#+u

#e!i,esis f&c,) +e),u#u%& !&$ se)u+& (e$& sel )#&l- PDGF "+l&,ele,-(e)i4e( $)0,% f&c,)* !&i,u f&c,) +e),u#u%& !&$ e)&s&l

(&)i ,)#si,  $lil&s,#&- TGF-Al+%& ",)&sf)#i$ $)0,% f&c,) &*  s&)'#&- Bee)&+& '&sus !&$ e)#&s&l&% &(&l&% +)(u' '$e "c/ RAS*

se%i$$& e's+)esi e)lei%& $e f&c,) +e),u#u%&  sel (i+&'s&

#e$elu&)'& se5u#l&% es&) f&c,) +e),u#u%&- 2,% $e !&$ #e$'(e %#l$ (&)i f&c,) +e),u#u%& 3)l&s, 5u$&

(&+&, (i,e#u'& (i ,u#) s&lu)& ce)& (& +&!u(&)& "c/ %s, 6 1 (& FGF

7*

•

Rese+,) f&c,) +e),u#u%&- R&$'&i& ,)&s(u'si si!&l #eli&,'& )ese+,) f&c,) +e),u#u%&- Bee)&+& '$e #e$'(e )ese+,) f&c,) +e),u#u%&- Di,e#u'& #u,&se (& e's+)esi e)lei%& +&,l$i' e,u' )#&l )ese+,)

f&c,) +e),u#u%&- P),ei )ese+,) #u,& #e!&lu)'& si!&l #i,$ei' ',iu 'e sel

0&l&u+u ,i(&' ,e)(&+&, f&c,) +e),u#u%& (i se'i,&)!&.

7/23/2019 Enam Perubahan Mendasar Dalam Fisiologi Sel Yang Menentukan Fenotipe Ganas

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- E's+)esi e)lei%& )ese+,) f&c,) +e),u#u%&  sel '&'e) e)e&'si

e)lei%& ,e)%&(&+ '&(&) )#&l f&c,) +e),u#u%& su&,u '&(&) !&$

i&s&!& ,i(&' #e#icu +)life)&si.- 2,%/ EGF "e+i(e)#&l $)0,% f&c,)* !&i,u f&c,) +e),u#u%& e+i(e)#is.

ERBB1 Rese+,) EGF #e$&l&#i e's+)esi e)lei%& +&(& 89: '&)si#& sel

s'u&#s& +&)u. A,&u HER; "ERBB;* #e$&l&#i &#+li3'&si +&(& ;<:-79:'&'e) +&!u(&)& (& &(e'&)si#& +&)u 4&)iu# (& 'ele5&) liu)

• P),ei ,)&s(u'si si!&l

- #u,&si $e !&$ #e$'(e e)&$&i '#+e (i 5&lu) +e$%&,&) si!&l- Mle'ul +e$%&,&) si!&l #e$%uu$'& )ese+,) f&c,) +e),u#u%& 'e

s&s&)&!& (i i,i sel.- P),ei se#&c&# ii e)%uu$& (e$& le#&) (&l&# #e)& +l&s#&

,e#+&, +),ei ii #ee)i#& si!&l (&)i )ese+,) f&c,) +e),u#u%& !&$

,el&% &',if (& #e!&lu)'& si!&l ,e)seu, 'e i,i sel.- Du& &$$,& +e,i$ (&l&# '&,&$)i ii/ RAS (& ABL.

- 79: ,u#) #e$&(u$ #u,& $e RAS "c/ ,i$$i +&(& '&'e) 'l (&+&c)e&s*o Me)u+&'& 'el&i& '$ei'

o Be)'&i,& (e$& u'le,i(& $u&si "$u&si ,)ifsf&, =GTP> (&

$u&ie (ifsf&, =GDP>*o P),ei RAS )#&l e)+i(&% l&' &li' &,&)& 'e&(&& ,e)e'si,&si

"#e!&lu)'& si!&l* (& 'e&(&& ,e&$ "i&',if*. P&(& 'e&(&&

i&',if RAS e)i'&,& (e$& GDP l&lu 'e,i'& (i)&$s&$ le% f&c,)

+e),u#u%& (& #e5&(i &',if RAS #eu'&) GDP #e5&(i GTP. L&lu

sel e)+)life)&si. A',i4i,&s i,)isic GTP&se !&$ 'e#u(i&

#e$%i()lisis GTP #e5&(i GDP 'e#&li. A',i4i,&s GTP&se +&(&

+),ei RAS (i+e)'u&, le% +),ei +e$&',if !&$ e)&#& GAPs.o GAPs &(&l&% )e# #lecul&) !&$ #ece$&% +e$&',i4& RAS ,&'

,e)',)l (e$& #e()$ %i()lisis GTP #e5&(i GDP.o RAS #u,& e)i'&,& (e$& GAPs ,e,&+i &',i4i,&s GTP&se ,i(&'

#ei$'&, se%i$$& RAS #u,& ,e)+e)&$'&+ (&l&# e,u' &',if.o H&sil #u,&se RAS &'& se)u+& (e$& #u,&se +&(& GAPs

o Mu,&si $e +e$%&sil RAS i&s&!& ,e)5&(i '&)e& #u,&se ,i,i' !&$

e)+us&, (i se'i,&) '( 1; 17 "&s&# &#i ,e)(&+&, (i '&,u$

+e$i'&, u,u' GTP* (& ?1 "#e$'(e )e$i essesi&l u,u'

%i()lisis GTP*- Ti)si 'i&se !&$ ,i(&' e)'&i,& (e$& )ese+,) 5u$& e)+e)& (&l&#

,)&s(u'si si!&l c,%!& &(&l&% ABL. ABL &!&' e)'&i,& (e$&'&)si$eesis

o P),$e ABL #e#ili'i &',i4i,&s ,i)si 'i&se !&$ (i%&#&, le%

(#&i )e$ul&,)i' e$&,i4e. @i'& ABL #e$&l&#i ,)&sl'&si (&)i

')#s# 'e ')#s# ;; $e ,e)seu, #e!&,u (e$& B2R

")e&'+i, clus,e) )e$i* #e5&(i B2R-ABL se%i$$& #e#ili'i

&',i4i,&s ,i)si 'i&se !&$ 'u&,  leu'e#i& #!eli( ')i'.

7/23/2019 Enam Perubahan Mendasar Dalam Fisiologi Sel Yang Menentukan Fenotipe Ganas

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ABL (&l&# i,i sel ,i(&' (&+&, #e()$

&++,sis +&(& sel !&$ #e$&l&#i 'e)us&'&

DNA '&)e& ,e),&%& (&l&# si,+l&s#&

- Se#u& 5&lu) ,)&s(u'si si!&l #&su' 'e i,i sel (& #ei#ul'& (&#+&'

+&(& se'u#+ul& $e )es+(e !&$ #e()$ sel #&su' 'e (&l&# si'lus

#i,,ic.- O'+),ei se+e),i/ MY2 MYB @UN FOS (& REL (&+&, (i ,e#+u'& (i i,i

sel !&$ #e$&l&#i #u,&se- MY2 +&li$ se)i$ ,e)li&, +&(& ,u#) #&usi&

o P),'$e MY2 (ie's+)esi'& +&(& %&#+i) se#u& sel (& +),ei.

o MY2 ce+&, #e$&l&#i i(u'si &+&il& sel !&$ ,i(&' &',if #e#el&%

#ee)i#& si!&l u,u' e)+)life)&sio P),ei MY2 e)i'&,& (e$& DNA #e!e&'& &',i4&si

,)&s')i+si&l ee)+& $e ,e)'&i, +e),u#u%& c,%/ e)&$&i

2DK "'i&se (e+e(e-si'li* !&$ +)(u'!& #e()$ sel #&su'

'e si'lus sel.o Sel )#&l/ MY2 ,u)u #e(e'&,i &s&l 'e,i'& si'lus sel (i#ul&i

o O'i' $e/ MY2 e)'&i,& (e$& e's+)esi $e !&$ #ee,&+ &,&u

e)lei%& se%i$$& e)+)life)&si ,e)us-#ee)us.o 2,%/ (is)e$ul&si  Li#f#& Bu)'i,, '&)e& ,)&s')i+si ,"81C* MY2.

  A#+li3'&si  K&'e) +&!u(&)& 'l +&)u

• Si'li (& 'i&se (e+e(e-si'li

- K&'e) (&+&, #e5&(i ,# &+&il& $e !&$ #e$$e)&''& si'lus sel#e$&l&#i (is)e$ul&si &'i&, #u,&se &,&u &#+li3'&si.

- Pe)5&l&& ,e)&,u) sel #el&lui e)&$&i f&se (i'e(&li'& le% 2DK !&$ ,el&%

&',if'& le% +e$i'&,&!& 'e f&#il! +),ei l&i (iseu, si'li- Te)(&+&, i%ii,) si'li !&$ 4e)fu$si #ee'& 2DK (& #ei#ul'&

',)l e$&,i4e ,e)%&(&+ si'lus sel. @eis!& !&i,u 2DKN1A (& !&$ #e#ili'i

efe' sele',if +&(& si'li D2DKC (& si'li D2DK? "+),ei INKC*- Mu,&si !&$ #e!e&'& (is)e$ul&si &',i4i,&s si'li (& 2DK &'&

#e#u(&%'& sel e)+)life)&si- 2,% #u,&si +&(&/

o E's+)esi e)lei%& si'li D/ '&'e) +&!u(&)& es+%&$us %&,i.

o A#+li3'&si $e 2DKC/ #el&#& s&)c#& $lil&s,#&

;. Isesi,i4i,&s ,e)%&(&+ si!&l +e$%&#&, +e),u#u%&- &l&u+u '$e #e#+)(u'si e)&$&i +),ei !&$ #e()$

+e),u#u%& sel ,e)(&+&, +)(u' $e +ee'& ,u#) !&$ #e5&(i )e#

&$i +)life)&si sel.

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- G&$$u& ,e)%&(&+ $e ii #e!e&'& sel )ef)&',e) ,e)%&(&+ i%iisi

+e),u#u%& (& #i)i+ (e$& efe' #e()$ +e),u#u%& '$e.- Ge RB ")e,il&s,#&* +),,!+e $e +ee'& sel '&'e),u#) !&$

+e),&#& '&li (i,e#u'& !&$ (i,e#u'& #el&lui +eeli,i& +&(& +e!&'i,

)e,il&s,#& su&,u ,u#) &&' !&$ 5&)&$ (i,e#u'&.

- Sec&)& +)isi+ si!&l &,i+e),u#u%& (&+&, #ece$&% +)life)&si sel #el&lui(u& #e'&is#e '#+le#e,e) !&i,u/

o Me!e&'& sel !&$ se(&$ #e#el&% #&su' 'e #&s& G9 ",e&$

o Me!e&'& sel #&su' 'e ,&%&+ +&sc&#i,,i' (& e)fe)esi&si se),&

'e%il&$& +,esi )e+li'&,if!&.

7. Me$%i(&)i &++,sis

C. A$i$eesis e)'el&5u,&

<. Ke#&#+u& #e$i4&si (& e)&&'se&)