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J Cancer 2020; 11(18):5490-5502. doi:10.7150/jca.46547 This issue Cite

Research Paper

Wnt5a regulates Ameloblastoma Cell Migration by modulating Mitochondrial and Cytoskeletal Dynamics

Xue Qiao^3,4*, Xing Niu^1*, Junxiu Shi⁵, Lijie Chen¹, Xiaobin Wang⁶, Jinwen Liu⁷, Li Zhu³, Ming Zhong^1,2✉

1. Department of Oral Histopathology, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
2. Department of Stomatology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
3. Department of Central Laboratory, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
4. Department of Oral Biology, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
5. Department of Developmental Cell Biology, Cell Biology Division, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning, China.
6. Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
7. Department of Periodontics, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
*These authors contributed equally to this work.

✉ Corresponding author: Ming Zhong, E-mail: mzhongedu.cn; Department of Oral Histopathology, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, No.117 North Nanjing Street, Shenyang 110002, Liaoning, China. Department of Stomatology, Xiang'an Hospital of Xiamen University, No.2000 Xiang'an East Road, Xiang'an District, Xiamen 361102, Fujian, China. More

Abstract

Objective: Abnormal expression of Wnt5a has been detected in various tumors, including ameloblastoma (AB). Yet, there is no specific mechanistic evidence for the functional role of Wnt5a in AB. In this study, we aimed to conduct a mechanistic examination of the importance of Wnt5a in AB development.

Methods: The expressions of Wnt5a and Coro1A were examined by Western blot and immunohistochemistry both in AB tissues and AM-1 cells. The number and size of mitochondria were detected by electronic transmission microscope and confocal microscope. Gain-of-function and loss-of-function assays were used to explore the biological roles of Wnt5a and Coro1A in organelle dynamics changes and cell migration. Cell migration was detected by wound healing and transwell assay.

Results: We found that in AM-1 cells, up-regulation of Wnt5a led to enhanced mitochondrial energy production and altered calcium homeostasis, with elevated calcium levels directly leading to altered mitochondrial dynamics and interactions between the cytoskeleton and the mitochondria. When Wnt5a or its downstream cytoskeleton-associated protein Coro1A was knocked down, the migration capacity of AM-1 cells was markedly impaired.

Conclusion: Together, these results suggest that Wnt5a plays mitochondria and cytoskeleton specific roles in regulating the development of human AB, with its down-regulation leading to impaired tumor development, thus highlighting Wnt5a or Coro1A as potentially viable therapeutic targets for the treatment of AB.

Keywords: ameloblastoma, mitochondria-cytoskeleton, Wnt5a, Coro1A, migration

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