ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
TNF-α Exacerbates Calcium Influx via Voltage-Gated Calcium Channels in Breast Cancer Cells: A Nanoscale Multimodal AFM Study
Provisionally accepted
Zhongwei Wang1Qianhui Xu2Huaiwei Zhang2Rongrong Feng2Junmei Chen2
Jinsong Wei1Haijian Zhong2
Weidong Zhao2*- 1Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- 2Gannan Medical University, Ganzhou, China
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Tumor necrosis factor-α (TNF-α) exacerbates calcium influx through voltage-gated calcium channels (VGCC), thereby inducing apoptosis and is supposed as a potential therapeutic strategy for cancers. However, the single molecular level mechanisms underlying TNF-α's effects remain unclear. This study employed multiple modes of Atomic Force Microscopy (AFM) to investigate TNF-α's impact on breast cancer cells at nanometer spatial resolution, picoNewton force sensitivity, picoAmpere current precision, and 0.1 mV surface potential accuracy. Results revealed that TNF-α treatment significantly increased the density and aggregation of VGCC on cell membranes while enhancing their channel activity. Concurrently, the electrical conductivity and surface potential of the membrane were elevated, collectively promoting exacerbated calcium influx. These findings elucidate the mechanisms by which TNF-α modulates VGCC distribution and electrophysiological properties to amplify calcium signaling, triggering apoptosis. The study provides unprecedented single molecule level insights into TNF-α induced calcium dysregulation in cancer cells, offering a novel approach for investigating apoptosis and advancing targeted therapies for breast cancer and other malignancies.
Keywords: Voltage gated calcium channel, TNF-α, Apoptosis, single-molecule mechanisms, Atomic Force Microscopy
Received: 23 May 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Wang, Xu, Zhang, Feng, Chen, Wei, Zhong and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Weidong Zhao, zhaowd@gmu.edu.cn
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