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.
Bibliographical noteFunding Information:
The skillful technical assistance of Anish Ashok Adpaikar (College of Dentistry Yonsei University) is gratefully acknowledged.
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF-2022R1A2B5B03001627 and NRF‐2016R1A5A2008630).
© 2022, The Author(s).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)