Metformin Induces Human Esophageal Carcinoma Cell Pyroptosis by Targeting the miR-497/PELP1 Axis

Document Type

Article

Publication Date

2-13-2019

Abstract

Evasion of apoptosis is a major contributing factor to the development of chemo- and radiotherapy resistance. Therefore, activation of non-apoptotic programmed cell death (PCD) could be an effective alternative against apoptosis-resistant cancers. In this study, we demonstrated in vitro and in vivo that metformin can induce pyroptosis, a non-apoptotic PCD, in esophageal squamous cell carcinoma (ESCC), a commonly known chemo-refractory cancer, especially at its advanced stages. Proline-, glutamic acid- and leucine-rich protein-1 (PELP1) is a scaffolding oncogene and upregulated PELP1 in advanced stages of ESCC is highly associated with cancer progression and patient outcomes. Intriguingly, metformin treatment leads to gasdermin D (GSDMD)-mediated pyroptosis, which is abrogated by forced expression of PELP1. Mechanistically, metformin induces pyroptosis of ESCC by targeting miR-497/PELP1 axis. Our findings suggest that metformin and any other pyroptosis-inducing reagents could serve as alternative treatments for chemo- and radiotherapy refractory ESCC or other cancers sharing the same pyroptosis mechanisms.

Publication Title

Cancer Letters

Volume

450

First Page

22

Last Page

31

PubMed ID

30771436

Comments

This article was published in Cancer Letters, Volume 450, pages 22-31.

The published version is available at https://doi.org/10.1016/j.canlet.2019.02.014.

Copyright © 2019 Elsevier B.V.

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