Inhibition of L-type voltage-gated calcium channel-mediated Ca2+ influx suppresses the collective migration and invasion of ameloblastoma

Shujin Li, Hyun Yi Kim, Dong Joon Lee, Sung Ho Park, Keishi Otsu, Hidemitsu Harada, Young Soo Jung, Han Sung Jung

Research output: Contribution to journalArticlepeer-review


Objectives: Ameloblastoma (AM) has been known as a benign but locally invasive tumour with high recurrence rates. Invasive behaviour of the AM results in destruction of the adjacent jawbone and the non-detectable remnants during surgery, interrupting the complete elimination of cancer cells. Methods: To explore novel targets for the tumour cell invasion, a transcriptomic analysis between AM and odontogenic keratocyst were performed through next-generation sequencing in detail. Results: Enrichment of CACNA1C gene (encoding Cav1.2) in AM, a subunit of the L-type voltage-gated calcium channel (VGCC) was observed for the first time. The expression and channel activity of Cav1.2 was confirmed by immunostaining and calcium imaging in the patient samples or primary cells. Verapamil, L-type VGCC blocker revealed suppression of the Ca2+-induced cell aggregation and collective invasion of AM cells in vitro. Furthermore, the effect of verapamil in suppressing AM invasion into the adjacent bone was confirmed through orthotopic xenograft model specifically. Conclusion: Taken together, Cav1.2 maybe considered to be a therapeutic candidate to decrease the collective migration and invasion of AM.

Original languageEnglish
Article numbere13305
JournalCell Proliferation
Issue number11
Publication statusPublished - 2022 Nov

Bibliographical note

Funding Information:
National Research Foundation of Korea, Grant/Award Numbers: NRF‐2016R1A5A2008630, NRF‐2022R1A2B5B03001627 Funding information

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF‐2022R1A2B5B03001627, NRF‐2016R1A5A2008630).

Publisher Copyright:
© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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