JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Simulated microgravity suppresses oral squamous cell carcinoma growth through Piezo1-mediated regulation of calcium ion homeostasis and the autophagy pathway

Author(s): Jian YUAN^1, Yi XU^1, Xiaocui LUO^2*, Xiaotong HE³, Yining LI¹, Chao JIANG⁴, Fan TANG¹, Shan WANG¹, Cunman HE⁵, Yaohui ZHU⁶, Lingkai SU¹, Hui LU⁷, Shangjun ZHANG¹, Yuliu LIN¹, Keyan JI¹, Zhiyong WANG¹, Zuchao CAI¹, Qianming CHEN¹
Affiliation(s): ¹Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China ²Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China, 100084; more
Corresponding email(s): Zhiyong WANG, wzy0809@zju.edu.cn Zuchao CAI, caizuchao@zju.edu.cn
Key Words: Simulated microgravity; Mechanotransduction; Autophagy; Mitophay; Oral squamous cell carcinoma; Calcium ion homeostasis; Piezo1

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Jian YUAN^1*, Yi XU^1*, Xiaocui LUO^2*, Xiaotong HE³, Yining LI¹, Chao JIANG⁴, Fan TANG¹, Shan WANG¹, Cunman HE⁵, Yaohui ZHU⁶, Lingkai SU¹, Hui LU⁷, Shangjun ZHANG¹, Yuliu LIN¹, Keyan JI¹, Zhiyong WANG¹, Zuchao CAI¹, Qianming CHEN¹. Simulated microgravity suppresses oral squamous cell carcinoma growth through Piezo1-mediated regulation of calcium ion homeostasis and the autophagy pathway[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500648

@article{title="Simulated microgravity suppresses oral squamous cell carcinoma growth through Piezo1-mediated regulation of calcium ion homeostasis and the autophagy pathway",
author="Jian YUAN^1*, Yi XU^1*, Xiaocui LUO^2*, Xiaotong HE³, Yining LI¹, Chao JIANG⁴, Fan TANG¹, Shan WANG¹, Cunman HE⁵, Yaohui ZHU⁶, Lingkai SU¹, Hui LU⁷, Shangjun ZHANG¹, Yuliu LIN¹, Keyan JI¹, Zhiyong WANG¹, Zuchao CAI¹, Qianming CHEN¹",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500648"
}

%0 Journal Article
%T Simulated microgravity suppresses oral squamous cell carcinoma growth through Piezo1-mediated regulation of calcium ion homeostasis and the autophagy pathway
%A Jian YUAN^1*
%A Yi XU^1*
%A Xiaocui LUO^2*
%A Xiaotong HE³
%A Yining LI¹
%A Chao JIANG⁴
%A Fan TANG¹
%A Shan WANG¹
%A Cunman HE⁵
%A Yaohui ZHU⁶
%A Lingkai SU¹
%A Hui LU⁷
%A Shangjun ZHANG¹
%A Yuliu LIN¹
%A Keyan JI¹
%A Zhiyong WANG¹
%A Zuchao CAI¹
%A Qianming CHEN¹
%J Journal of Zhejiang University SCIENCE B
%P
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2500648"

TY - JOUR
T1 - Simulated microgravity suppresses oral squamous cell carcinoma growth through Piezo1-mediated regulation of calcium ion homeostasis and the autophagy pathway
A1 - Jian YUAN^1*
A1 - Yi XU^1*
A1 - Xiaocui LUO^2*
A1 - Xiaotong HE³
A1 - Yining LI¹
A1 - Chao JIANG⁴
A1 - Fan TANG¹
A1 - Shan WANG¹
A1 - Cunman HE⁵
A1 - Yaohui ZHU⁶
A1 - Lingkai SU¹
A1 - Hui LU⁷
A1 - Shangjun ZHANG¹
A1 - Yuliu LIN¹
A1 - Keyan JI¹
A1 - Zhiyong WANG¹
A1 - Zuchao CAI¹
A1 - Qianming CHEN¹
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2500648"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer, with metastasis significantly contributing to its poor prognosis. Emerging research indicates that microgravity may exert anti-tumor effects by inducing cell death, although the precise mechanisms remain unclear. Methods: The Rotary Cell Culture System (RCCS) was used to simulate microgravity, enabling observation of its effects on tumor cell proliferation and migration. Key genes and pathways influenced by simulated microgravity were identified using RNA sequencing (RNA-seq). In the tongue load-bearing tumor mouse model, we used hindlimb unloading (HU) to simulate microgravity and investigate its impact on tumor growth, and to validate the involvement of identified key genes and pathways. Results: Simulated microgravity induced significant morphological changes in OSCC cells, leading to the formation of multicellular spheroids and altering their biological behavior. RNA sequencing identified PIEZO1 as a key mechanosensitive gene upregulated under microgravity, along with the activation of autophagy-related pathways. In vivo experiments using a tongue load-bearing mouse model demonstrated that simulated microgravity suppressed tumor growth, which was associated with enhanced autophagy and disrupted calcium homeostasis. Piezo1 inhibition partially reversed these effects, confirming its critical role in microgravity-induced OSCC suppression. Conclusions: Simulated microgravity suppresses OSCC growth through Piezo1-mediated calcium dysregulation and enhanced mitophagy. Inhibition of Piezo1 reverses these effects, indicating its potential as a therapeutic target. This study highlights microgravity-based approaches as promising strategies for the treatment of OSCC.

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