2. Academic Validation
  3. Piezo1 activation using Yoda1 inhibits macropinocytosis in A431 human epidermoid carcinoma cells

Piezo1 activation using Yoda1 inhibits macropinocytosis in A431 human epidermoid carcinoma cells

  • Sci Rep. 2022 Apr 15;12(1):6322. doi: 10.1038/s41598-022-10153-8.
Masashi Kuriyama  # 1,  Hisaaki Hirose  # 2,  Toshihiro Masuda 1,  Masachika Shudou 3,  Jan Vincent V Arafiles 1,  Miki Imanishi 1,  Masashi Maekawa 4 5 6,  Yuji Hara 7 8,  Shiroh Futaki 9
Affiliations

Affiliations

  • 1 Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan.
  • 2 Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan. [email protected].
  • 3 Division of Analytical Bio-Medicine, Advanced Research Support Center, Ehime University, Toon, Ehime, 791-0295, Japan.
  • 4 Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Ehime, 791-0295, Japan.
  • 5 Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan.
  • 6 Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, 105-8512, Japan.
  • 7 Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto, 615-8510, Japan.
  • 8 School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
  • 9 Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan. [email protected].
  • # Contributed equally.
PMID: 35428847 DOI: 10.1038/s41598-022-10153-8
Abstract

Macropinocytosis is a type of endocytosis accompanied by actin rearrangement-driven membrane deformation, such as lamellipodia formation and membrane ruffling, followed by the formation of large vesicles, macropinosomes. Ras-transformed Cancer cells efficiently acquire exogenous Amino acids for their survival through macropinocytosis. Thus, inhibition of macropinocytosis is a promising strategy for Cancer therapy. To date, few specific agents that inhibit macropinocytosis have been developed. Here, focusing on the mechanosensitive ion channel Piezo1, we found that Yoda1, a Piezo1 agonist, potently inhibits macropinocytosis induced by epidermal growth factor (EGF). The inhibition of ruffle formation by Yoda1 was dependent on the extracellular Ca2+ influx through Piezo1 and on the activation of the calcium-activated Potassium Channel KCa3.1. This suggests that Ca2+ ions can regulate EGF-stimulated macropinocytosis. We propose the potential for macropinocytosis inhibition through the regulation of a mechanosensitive channel activity using chemical tools.

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