FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway

Yin Liyang; Cao Renxian; Liu Zhuoqing; Luo Gang; Li Yu; Zhou Xiaolong; Chen Xiguang; Wu Ying; He Jun; Zu Xuyu; Shen Yingying

doi:10.3724/abbs.2023142

Acta Biochimica et Biophysica Sinica (Sep 2023)

FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway

Yin Liyang,
Cao Renxian,
Liu Zhuoqing,
Luo Gang,
Li Yu,
Zhou Xiaolong,
Chen Xiguang,
Wu Ying,
He Jun,
Zu Xuyu,
Shen Yingying

Affiliations

Yin Liyang: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Cao Renxian: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Liu Zhuoqing: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Luo Gang: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Li Yu: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Zhou Xiaolong: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Chen Xiguang: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Wu Ying: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
He Jun: ["Nanhua Affiliated Hospital, Department of Spine Surgery, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Zu Xuyu: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]
Shen Yingying: ["The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China"]

DOI: https://doi.org/10.3724/abbs.2023142
Journal volume & issue: Vol. 55
pp. 1770 – 1783

Abstract

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Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3β and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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