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Unraveled roles of Cav1.2 in proliferation and stemness of ameloblastoma

 Shujin Li  ;  Dong-Joon Lee  ;  Hyun-Yi Kim  ;  Jun-Young Kim  ;  Young-Soo Jung  ;  Han-Sung Jung 
 CELL AND BIOSCIENCE, Vol.12(1) : 145, 2022-09 
Journal Title
Issue Date
Ameloblastoma ; Calcium signaling ; Cav1.2 ; Proliferation ; Stemness
Background: Transcriptome analysis has been known as a functional tool for cancer research recently. Mounting evidence indicated that calcium signaling plays several key roles in cancer progression. Despite numerous studies examining calcium signaling in cancer, calcium signaling studies in ameloblastoma are limited.

Results: In the present study, comparative transcriptome profiling of two representative odontogenic lesions, ameloblastoma and odontogenic keratocyst, revealed that Cav1.2 (CACNA1C, an L-type voltage-gated calcium channel) is strongly enriched in ameloblastoma. It was confirmed that the Ca2+ influx in ameloblastoma cells is mainly mediated by Cav1.2 through L-type voltage-gated calcium channel agonist and blocking reagent treatment. Overexpression and knockdown of Cav1.2 showed that Cav1.2 is directly involved in the regulation of the nuclear translocation of nuclear factor of activated T cell 1 (NFATc1), which causes cell proliferation. Furthermore, a tumoroid study indicated that Cav1.2-dependent Ca2+ entry is also associated with the maintenance of stemness of ameloblastoma cells via the enhancement of Wnt/β-catenin signaling activity.

Conclusion: In conclusion, Cav1.2 regulates the NFATc1 nuclear translocation to enhance ameloblastoma cell proliferation. Furthermore, Cav1.2 dependent Ca2+ influx contributes to the Wnt/β-catenin activity for the ameloblastoma cell stemness and tumorigenicity. Our fundamental findings could have a major impact in the fields of oral maxillofacial surgery, and genetic manipulation or pharmacological approaches to Cav1.2 can be considered as new therapeutic options.
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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
Kim, Jun-Young(김준영) ORCID logo https://orcid.org/0000-0002-6596-6135
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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