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Title 

Pyruvate kinase isoenzyme M2 is a therapeutic target of gemcitabine-resistant pancreatic cancer cells

Authors 

Dong Joon KimY S ParkM G KangYeon Mi YouYuri JungHan KooJung Ae KimM J KimS M HongK B LeeJ J JangKyung Chan ParkYoung Il Yeom

Publisher 

Elsevier

Issue Date 

2015

Citation 

Experimental Cell Research, vol. 336, no. 1, pp. 119-129

Keywords 

ApoptosisGemcitabinep53Pancreatic cancerPKM2

Abstract 

Despite its wide use as a first-line therapeutic agent, gemcitabine has shown limited efficacy in advanced pancreatic cancer due to chemoresistance by as yet unidentified mechanisms. Our goal here was to identify molecular features involved in gemcitabine chemoresistance. Pyruvate kinase M2 (PKM2), a key enzyme of aerobic glycolysis, has recently emerged as an important therapeutic target for cancer treatment. It is involved in the metabolic reprogramming of cancer cells and has previously unexpected non-metabolic functions that are heavily involved in tumor growth and survival. Herein, we report that the chemoresistance of pancreatic cancer to gemcitabine was dependent on PKM2 expression and its non-metabolic function. Knocking-down of PKM2 significantly enhanced gemcitabine-induced cell apoptosis through the activation of caspase 3/7 and PARP cleavage, and this inhibitory activity was associated with p38-mediated activation of p53 phosphorylation at serine 46. Our findings support the potential of PKM2 as a novel target for gemcitabine chemoresistance and suggest the feasibility of combining gemcitabine and PKM2 inhibition for the improved chemotherapy of pancreatic cancer.

ISSN 

0014-4827

Link 

http://dx.doi.org/10.1016/j.yexcr.2015.05.017

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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