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Ferroptosis is a lysosomal cell death process.

Abstract：

:Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation. While impaired ferroptosis is tightly linked to human diseases and conditions, the mechanism and regulation of ferroptosis remain largely unknown. Here, we demonstrate that STAT3 is a positive regulator of ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cell lines. Activation of the MAPK/ERK pathway, but not inhibition of system Xc-, was required for STAT3 activation during erastin-induced ferroptosis. Importantly, pharmacological inhibition and genetic silencing of STAT3 through small molecules (e.g., cryptotanshinone and S3I-201) or siRNA blocked erastin-induced ferroptosis in PDAC cells. Mechanically, STAT3-mediated cathepsin B expression was required for ferroptosis. Consequently, inhibition of lysosome-dependent cell death by pharmacological blockade of cathepsin activity (using CA-074Me) or vacuolar type H+-ATPase (using bafilomycin A1) limited erastin-induced ferroptosis. These studies indicate that ferroptosis is a lysosomal cell death process.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Gao H,Bai Y,Jia Y,Zhao Y,Kang R,Tang D,Dai E

doi

10.1016/j.bbrc.2018.07.078

subject

Has Abstract

pub_date

2018-09-10 00:00:00

pages

1550-1556

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)31574-2

journal_volume

503

pub_type

杂志文章

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