Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in
Nan Sook Lee1, Chi Woo Yoon1, Qing Wang2
1Ultrasonic Transducer Resource Center, Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States.
Frontiers in Cell and Developmental Biology
|July 14, 2020
Summary
Focused ultrasound (FUS) activates calcium signaling in invasive cancer cells by stimulating the PANX1 channel. This non-invasive technology may enhance cancer immunotherapy by promoting cytokine release.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Focused ultrasound (FUS) is an emerging non-invasive technology with therapeutic potential.
- FUS can modulate cellular processes, including calcium signaling, particularly in invasive cancer cells.
Purpose of the Study:
- To identify the molecular mechanisms underlying FUS-induced calcium signaling in invasive cancer cells.
- To investigate the role of the PANX1 channel in FUS-mediated cellular responses.
- To explore the potential of FUS as an adjuvant cancer therapy.
Main Methods:
- Utilized FUS stimulation on invasive and non-invasive cancer cell lines.
- Performed PANX1 knockdown and overexpression experiments.
- Measured intracellular calcium levels and ATP release.
- Assessed cytokine and chemokine release.
Main Results:
- FUS stimulation specifically activated calcium signaling in invasive cancer cells.
- PANX1 was identified as a key mediator; its knockdown reduced FUS-induced calcium signaling, while overexpression enhanced it in non-invasive cells.
- FUS directly stimulated endoplasmic reticulum-localized PANX1, independent of the cytoskeleton or plasma membrane.
- Plasma membrane PANX1 mediated intercellular calcium waves via ATP release.
- FUS evoked cytokine/chemokine release from invasive cancer cells.
Conclusions:
- PANX1 is a crucial mechanosensor for FUS-induced calcium signaling in invasive cancer cells.
- FUS can modulate cellular functions through direct PANX1 stimulation, offering new therapeutic avenues.
- FUS-evoked cytokine/chemokine release suggests potential as an adjuvant for cancer immunotherapy.
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