Localized heat induces ERK activation and signal propagation in solid tumors
Localized plasmonic heating by metallic nanoparticles offers a promising strategy to destroy cancer cells through controlled thermal stress. However, how cells sense and respond to microscale temperature variations within complex tissue environments remains unclear. Here, we investigate how plasmon-induced local heating reshapes intercellular signaling and cell fate within tumor spheroids, focusing on the extracellular signal-regulated kinase (ERK) pathway. HeLa spheroids expressing a FRET-based ERK biosensor were subjected to defined photothermal stimuli using gold nanostars as nanoscale heat sources, while ERK activity was tracked with a deep-learning algorithm (3DeeCellTracker). Local heating triggered marked alterations in ERK signaling dynamics compared to spontaneous activity, including changes in activation frequency, timing, and duration. Remarkably, heat-induced ERK activation spread across neighboring cells, revealing thermally mediated intercellular propagation. Quantitative analysis further showed that temperature elevation modulates cell death and division in a power-dependent manner. These results uncover how nanoscale heat generation governs signaling networks and collective cellular behavior, providing a mechanistic framework to understand and optimize heat-based cancer treatment strategies.
Authors
- Sayuki Hirano (ORCID: https://orcid.org/0000-0001-7183-6604)
- Kohei Otomo (ORCID: https://orcid.org/0000-0002-5322-6295)
- Chentao Wen (ORCID: https://orcid.org/0000-0002-8609-476X)
- Beatrice Fortuni (ORCID: https://orcid.org/0000-0003-4634-9518)
- Tomomi Nemoto (ORCID: https://orcid.org/0000-0001-6102-1495)
- Indra Van Zundert (ORCID: https://orcid.org/0000-0002-9975-6902)
- Motosuke Tsutsumi (ORCID: https://orcid.org/0000-0002-5832-3828)
- Kenji Hirai (ORCID: https://orcid.org/0000-0003-3307-3970)
- Farsai Taemaitree (ORCID: https://orcid.org/0000-0003-0295-9226)
- Yudai Yamashita
- Koutarou D. Kimura (ORCID: https://orcid.org/0000-0002-3359-1578)
- Daisuke Yamaguchi (ORCID: https://orcid.org/0000-0002-1147-6093)
- Sandra Krzyzowska (ORCID: https://orcid.org/0000-0003-4436-1564)
- Kazushi Yamaguchi
- Maria Bravo
- James Hutchison
- Yuta Takano
- Kazuhiro Aoki
- Hiroshi Uji-I
- Susana Rocha
Institutions
- Hokkaido University of Science (JP)
- The University of Melbourne (AU)
- National Institutes of Natural Sciences (JP)
- Tohoku University (JP)
- Hokkaido University (JP)
- Kyoto University (JP)
- Nagoya City University (JP)
- Juntendo University (JP)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Hokkai Gakuen University (JP)
- KU Leuven (BE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1038/s41598-026-49009-w
- Primary Topic
- Photoacoustic and Ultrasonic Imaging
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering
- Japan Society for the Promotion of Science