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Inhibition of L-type voltage-gated calcium channel-mediated Ca 2+ 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 
 CELL PROLIFERATION, : epub, 2022-07 
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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.
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Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Lee, Dong Joon(이동준) ORCID logo https://orcid.org/0000-0001-6532-9729
Jung, Young Soo(정영수) ORCID logo https://orcid.org/0000-0001-5831-6508
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
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