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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Pharmacol
2017 ; 8
(ä): 476
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Proteasome Inhibitor YSY01A Abrogates Constitutive STAT3 Signaling via
Down-regulation of Gp130 and JAK2 in Human A549 Lung Cancer Cells
#MMPMID28883791
Huang W
; Yuan X
; Sun T
; Fan S
; Wang J
; Zhou Q
; Guo W
; Ran F
; Ge Z
; Yang H
; Li R
; Cui J
Front Pharmacol
2017[]; 8
(ä): 476
PMID28883791
show ga
Proteasome inhibition interfering with many cell signaling pathways has been
extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor
YSY01A is a novel agent that has shown remarkable anti-tumor effects; however,
its mechanisms of action are not fully understood. Here we report that YSY01A is
capable of suppressing cancer cell survival by induction of apoptosis.
Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via
proteasome-independent degradation of gp130 and JAK2, but not transcriptional
regulation, in human A549 non-small cell lung cancer cells. The reduction in
gp130 and JAK2 can be restored by co-treatment with 3-methyladenine, an
early-stage autophagy lysosome and type I/III PI3K inhibitor. YSY01A also
effectively inhibits cancer cell migration and lung xenograft tumor growth with
little adverse effect on animals. Thus, our findings suggest that YSY01A
represents a promising candidate for further development of novel anticancer
therapeutics targeting the proteasome.