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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Silencing MFHAS1 Induces Pyroptosis via the JNK-activated NF-κB/Caspase1/ GSDMD Signal Axis in Breast Cancer

Author(s): Yue Jin, Mingrui Zhai, Rongyi Cao, Hongmin Yu, Chunli Wu and Yanhong Liu*

Volume 29, Issue 42, 2023

Published on: 02 November, 2023

Page: [3408 - 3420] Pages: 13

DOI: 10.2174/0113816128268130231026054649

Abstract

Introduction: Breast cancer has emerged as the most widespread cancer globally surpassing lung cancer, and has become a primary cause of mortality among women. While MFHAS1 has been implicated in the pathophysiology of various diseases, its precise involvement in breast cancer remains unclear.

Methods: This study endeavors to elucidate the regulatory function of MFHAS1 in breast cancer cell pyroptosis and the associated molecular mechanisms. Our findings indicate that the inhibition of MFHAS1 can impede the proliferation and invasion of breast cancer cells, while also inducing cell pyroptosis via caspase1-dependent activation of GSDMD.

Results: This process results in the cleavage of cell membranes, leading to the release of inflammatory factors and LDH. Subsequent investigations revealed that the silencing of MFHAS1 can promote JNK phosphorylation, thereby activating the JNK signaling cascade. Notably, this effect can be counteracted by the JNK-specific inhibitor sp600125. Ultimately, our investigation substantiated the identical function of MFHAS1 in breast cancer tissue derived from animal models.

Conclusion: To summarize, our findings demonstrate that the inhibition of MFHAS1 elicits pyroptosis in human breast cancer cells through the facilitation of JNK phosphorylation and the activation of the downstream NF-κB/caspase-1/GSDMD signaling cascade, thereby proposing the prospect of MFHAS1 as a viable therapeutic target for breast cancer.

Keywords: Breast cancer, pyroptosis, MFHAS1, JNK, caspase-1, lung cancer.

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