NEUREGULIN PROMOTES INCOMPLETE AUTOPHAGY OF PROSTATE CANCER CELLS

THAT IS INDEPENDENT OF MTOR PATHWAY INHIBITION

Ace Allawan, Kara Marcella Barro, John Oscar Enriquez, Eliezer Galope, Freece Angelo Rosalia,
Ulomoddin ilongan and Marianne Kris!elle "arra
B#O $%& ' Group ( March $), %&$*
+his s!ud, -ocused on !racing !he di--eren! pa!hwa,s, su.s!ances, su.!ra!es or ligands !ha! ma,
a--ec! !he au!ophag, o- pros!a!e cancer cells/ Au!ophag, is a mechanism o- !he cancer cells in which !he,
-eed !hemsel0es wi!h d,s-unc!ional organelles and pro!eins !o sur0i0e !he amino acid depri0a!ion, caused
., !herap, done !o pros!a!e cancer pa!ien!s -or e1ample/
2euregulin 32RG4 is a ligand o- Er.B56 recep!or !ha! is lin7ed !o human cancers/ 2RG was
s!udied in !his e1perimen! as !his ligand was 7nown !o inhi.i! grow!h o- !he androgen dependen! 829a:
pros!a!e cancer cells/ +hese 829a: cells are androgen5sensi!i0e human pros!a!e adenocarcinoma cells/
+hus, wi!h !his 7nown -ac!, a possi.le pa!hwa, can .e !raced -rom !he ligand 2RG !o i!s e--ec! on !he
829a: cells/
A-!er se0eral e1perimen!s done, !he researchers -ound !ha! !here are di--eren! su.s!ances or
su.s!ra!es !ha! induce and inhi.i! au!ophag, o- 829a: cells/ 2RG, in !he a.sence o- androgen, induces
dea!h o- 829a: cells and media!es au!ophag,/ Au!ophag, in 829a: is inhi.i!ed ., *5me!h,ladenine 3*5
MA4, Ba-ilom,cin ' A$, 25ace!,lec,s!eine 32A94, J2K inhi.i!or and Bcl5% .ound !o Beclin $/ *5MA is
a :#*K inhi.i!or was -ound !o inhi.i! au!ophag, in 829a: cells using !he 89* pro!ein as a mar7er/
Ba-ilom,cin ' A$ inhi.i!s au!ophagosome5l,sosome -usion which is a par! o- !he process o- au!ophag,/
;hen au!ophagosome does no! -uses wi!h l,sosome, !he organelles and pro!eins enclosed ., !he
au!ophagosome will no! .e degraded ., !he l,sosome, no -ood will .e -ormed -or !he cells, au!ophag, is
.loc7ed/ 2A9 is an an!io1idan! !ha! a.olished !he -orma!ion o- au!ophagosomes !hus inhi.i!ed 2RG5
induced au!ophag, and cell dea!h/ J2K is responsi.le -or response !o s!imuli/ #! was -ound !ha! J2K is a
po!en!ial media!or o- 2RG5induced au!ophag,, !hus J2K inhi.i!or clearl, inhi.i!s au!ophag,/ 8as!l,,
.eclin $ is a ma<or 7nown regula!or o- au!ophag,, howe0er when .ound !o Bcl5% 3an an!i5apop!o!ic
pro!ein4, !he au!ophagic ac!i0i!, o- .eclin $ is inhi.i!ed/
On !he o!her hand, reac!i0e o1,gen species 3RO4, ac!i0a!ion o- J2K pa!hwa,, .eclin $,
rapam,cin and inac!i0a!ion o- m+OR pa!hwa, induce au!ophag, in 829a: cells/ RO pla,s a role in
au!ophag, .ecause i! is required -or s!ar0a!ion5induced au!ophag, and i! is 7nown !o induce au!ophag,
in cer!ain cell lines/ As a con!radic!ion !o !he s!a!emen!s men!ioned a.o0e, ac!i0a!ion o- J2K pa!hwa,
and .eclin $ induce 829a: cells au!ophag,/ Rapam,cin is an m+OR inhi.i!or !ha! downregula!es !he
m+OR ac!i0i!,/ m+OR is a nega!i0e regula!or o- au!ophag,, !hus when !his pa!hwa, is inhi.i!ed,
au!ophag, is ac!i0a!ed/ m+OR pa!hwa, is !he po!en!ial pa!hwa, !ha! !he signals -rom 2RG ma, cross
or -ollow -or !he au!ophag, o- 829a: cells/ 2RG !rea!men! increased !he le0el o- phosphor,la!ion o-
A7! 3ac!i0a!es !he m+OR4, howe0er i! is -ound !o .e incomple!e .ecause inac!i0a!ion o- !his pa!hwa,
had no e--ec! on !he phosphor,la!ion le0els o- !he A7!/ +hus, i! was concluded !ha! neuregulin promo!es
incomple!e au!ophag, o- pros!a!e cancer cells which is independen! on !he m+OR pa!hwa, inhi.i!ion/
;i!h !his in-orma!ion, !his s!ud, can pro0ide insigh!s on !rea!ing pros!a!e cancer ., !arge!ing !he
pa!hwa, !ha! ma, inhi.i! !he au!ophag, o- cancer cells -or !hem no! !o sur0i0e/ ;hen !he cancer cells
are comple!el, depri0ed wi!h !he amino acid or -ood !he, need, one ma, !arge! !hese cells and 7ill !hem/
#! will .e a grea! con!ri.u!ion !o science as !rea!men! !o cancer will .e disco0ered/ =owe0er, more
research mus! .e done !o comple!el, !race !he pa!hwa,/