Chemical activation of Piezo1 to enhance TRAIL-mediated apoptosis in glioblastoma cells

Authors

Samantha Knoblauch¹ , Shanay Desai¹ , Jenna Dombroski¹ , Nicole Sarna¹ , Jacob Hope¹ , Michael King¹

1. Vanderbilt University

Conference / event

Biomedical Engineering Society 2022 Annual Meeting, October 2022 (San Antonio, TX, United States)

Poster summary

Glioblastoma multiforme (GBM) treatment with the current standard of care, temozolomide (TMZ), may be ineffective if damaged tumor cells undergo DNA repair or acquire mutations that inactivate transcription factor p53, leading to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in multiple tumor types through a transcription-independent mechanism. GBM is particularly resistant to TRAIL, but studies have found that activation of the mechanoreceptor Piezo1 can induce TRAIL sensitization in other cancer cell lines. This study examines the effects and mechanism of Piezo1 chemical activation via Yoda1 on TRAIL-mediated apoptosis in GBM. We demonstrate that a Yoda1 + TRAIL combination therapy significantly increases apoptosis in two GBM cell lines. Further, cells known to be resistant to TMZ had higher levels of Piezo1 expression and were more susceptible to our treatment. The results of this study demonstrate the efficacy of overcome TMZ resistance in GBM using TRAIL and Piezo1 activation.

Keywords

Apoptosis, Assays, Cancer, Cells, Polarization, Mechanobiology

Research areas

Bioengineering, Biological Sciences

References

No data provided

Funding

1. National Institutes of Health (No. CA256054)

Supplemental files

No data provided

Additional information

Competing interests

No competing interests were disclosed.

Data availability statement

The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.

Creative Commons license

Copyright © 2023 Knoblauch et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.