Open AccessInhibition of L‐type voltage‐gated calcium channel‐mediated Ca 2+ influx suppresses the collective migration and invasion of ameloblastoma
Author(s) -
Li Shujin,
Kim HyunYi,
Lee DongJoon,
Park SungHo,
Otsu Keishi,
Harada Hidemitsu,
Jung YoungSoo,
Jung HanSung
Publication year - 2022
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13305
Subject(s) - calcium , biophysics , chemistry , voltage dependent calcium channel , channel (broadcasting) , l type calcium channel , calcium channel , ameloblastoma , microbiology and biotechnology , biology , anatomy , computer science , telecommunications , maxilla , organic chemistry
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 Ca 2+ ‐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.