Detailed Information

Cited 0 time in webofscience Cited 14 time in scopus
Metadata Downloads

Kallikrein-related peptidase 6 induces chemotherapeutic resistance by attenuating auranofin-induced cell death through activation of autophagy in gastric canceropen access

Authors
Kim, Tae WooLee, Seon-JinKim, Jong-TaeKim, Sun JungMin, Jeong-KiBae, Kwang-HeeJung, HaiyoungKim, Bo-YeonLim, Jong-SeokYang, YoungYoon, Do-YoungChoe, Yong-KyungLee, Hee Gu
Issue Date
Nov-2016
Publisher
IMPACT JOURNALS LLC
Keywords
kallikrein-related peptidase 6; autophagy; auranofin; cell death; chemoresistance
Citation
ONCOTARGET, v.7, no.51, pp 85332 - 85348
Pages
17
Journal Title
ONCOTARGET
Volume
7
Number
51
Start Page
85332
End Page
85348
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9334
DOI
10.18632/oncotarget.13352
ISSN
1949-2553
Abstract
Kallikrein-related peptidase 6 (KLK6) is a biomarker of gastric cancer associated with poor prognosis. Mechanisms by which KLK6 could be exploited for chemotherapeutic use are unclear. We evaluated auranofin (AF), a compound with cytotoxic effects, in KLK6-deficient cells, and we investigated whether KLK6 expression induces autophagy and acquisition of drug resistance in gastric cancer. Using cultured human cells and a mouse xenograft model, we investigated how KLK6 affects antitumor-reagent-induced cell death and autophagy. Expression levels of KLK6, p53, and autophagy marker LC3B were determined in gastric cancer tissues. We analyzed the effects of knockdown/overexpression of KLK6, LC3B, and p53 on AF-induced cell death in cancer cells. Increased KLK6 expression in human gastric cancer tissues and cells inhibited AF-induced cell motility due to increased autophagy and p53 levels. p53 dependent induction of KLK6 expression increased autophagy and drug resistance, whereas KLK6 silencing decreased the autophagy level and increased drug sensitivity. During AF-induced cell death, KLK6 and LC3B colocalized to autophagosomes, associated with p53, and were then trafficked to the cytosol. In the xenograft model of gastric cancer, KLK6 expression decreased AF-induced cell death and KLK6-induced autophagy increased AF resistance. Taken together, the data suggest that the induction of autophagic processes through KLK6 expression may increase acquisition of resistance to AF. Our findings may contribute to a new paradigm for tumor therapeutics.
Files in This Item
Go to Link
Appears in
Collections
이과대학 > 생명시스템학부 > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Yang, Young photo

Yang, Young
이과대학 (생명시스템학부)
Read more

Altmetrics

Total Views & Downloads

BROWSE