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Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells

Authors
  • Lee, Nan Sook1
  • Yoon, Chi Woo1
  • Wang, Qing2
  • Moon, Sunho1
  • Koo, Kweon Mo1
  • Jung, Hayong1
  • Chen, Ruimin1
  • Jiang, Laiming1
  • Lu, Gengxi1
  • Fernandez, Antony3
  • Chow, Robert H.4
  • Weitz, Andrew C.1
  • Salvaterra, Paul M.5
  • Pinaud, Fabien6
  • Shung, K. Kirk1
  • 1 Ultrasonic Transducer Resource Center, Department of Biomedical Engineering, University of Southern California, Los Angeles, CA , (United States)
  • 2 Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou , (China)
  • 3 Department of Biological Sciences, University of Southern California, Los Angeles, CA , (United States)
  • 4 Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA , (United States)
  • 5 Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA , (United States)
  • 6 Department of Biological Sciences, Chemistry and Physics & Astronomy, University of Southern California, Los Angeles, CA , (United States)
Type
Published Article
Journal
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Publication Date
Jun 23, 2020
Volume
8
Identifiers
DOI: 10.3389/fcell.2020.00504
PMID: 32656213
PMCID: PMC7325310
Source
PubMed Central
Keywords
License
Unknown

Abstract

Focused ultrasound (FUS) is a rapidly developing stimulus technology with the potential to uncover novel mechanosensory dependent cellular processes. Since it is non-invasive, it holds great promise for future therapeutic applications in patients used either alone or as a complement to boost existing treatments. For example, FUS stimulation causes invasive but not non-invasive cancer cell lines to exhibit marked activation of calcium signaling pathways. Here, we identify the membrane channel PANNEXIN1 (PANX1) as a mediator for activation of calcium signaling in invasive cancer cells. Knockdown of PANX1 decreases calcium signaling in invasive cells, while PANX1 overexpression enhances calcium elevations in non-invasive cancer cells. We demonstrate that FUS may directly stimulate mechanosensory PANX1 localized in endoplasmic reticulum to evoke calcium release from internal stores. This process does not depend on mechanosensory stimulus transduction through an intact cytoskeleton and does not depend on plasma membrane localized PANX1. Plasma membrane localized PANX1, however, plays a different role in mediating the spread of intercellular calcium waves via ATP release. Additionally, we show that FUS stimulation evokes cytokine/chemokine release from invasive cancer cells, suggesting that FUS could be an important new adjuvant treatment to improve cancer immunotherapy.

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