Int J Biol Sci 2022; 18(1):112-123. doi:10.7150/ijbs.63388 This issue

Research Paper

Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation

Yujie Huang1#, Ruijuan Liu1#, Xuechao Han1#, Xiaoyan Hou1, Yonghao Tian2, Weifang Zhang1✉

1. Department of Microbiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
2. Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong, China.
#These authors contributed equally to this work.

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Citation:
Huang Y, Liu R, Han X, Hou X, Tian Y, Zhang W. Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation. Int J Biol Sci 2022; 18(1):112-123. doi:10.7150/ijbs.63388. Available from https://www.ijbs.com/v18p0112.htm

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Abstract

Graphic abstract

Persistent infection with high-risk human papillomavirus (HPV) is the main risk factor for cervical cancer. Our mass spectrometry data showed that the Ras-associated binding protein Rab31 was upregulated by HPV; however, little is known regarding the role of Rab31 in the metastasis of cervical cancer cells. In this study, we showed that Rab31 was highly expressed in cervical cancer tissues and cells, and both HPV E6 and E7 promoted the expression of Rab31. Rab31 knockdown inhibited while Rab31 overexpression promoted the migration and invasion capabilities of cervical cancer cells. Additionally, Rab31 knockdown inhibited the epithelial-mesenchymal transition (EMT) and cytoskeletal rearrangement in cervical cancer cells. Furthermore, Rab31 interacted with mitogen-activated protein kinase 6 (MAPK6), and Rab31 knockdown inhibited the expression of MAPK6, which was mainly localized in the cytoplasm. More importantly, Rab31 knockdown promoted and Rab31 overexpression inhibited MAPK6 degradation. Accordingly, MAPK6 overexpression restored the decreased migration potential caused by Rab31 knockdown. Finally, a xenograft mouse model showed that Rab31 knockdown in cervical cancer cells led to reduced tumor growth and impaired lung and liver metastasis in vivo. In conclusion, Rab31 plays a crucial role in cervical cancer metastasis by inhibiting MAPK6 degradation. Thus, Rab31 may serve as a novel therapeutic target to manage cervical cancer.

Keywords: Cervical cancer, HPV, Rab31, MAPK6, Metastasis