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

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 cance...

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Veröffentlicht in:International journal of biological sciences 2022, Vol.18 (1), p.112-123
Hauptverfasser: Huang, Yujie, Liu, Ruijuan, Han, Xuechao, Hou, Xiaoyan, Tian, Yonghao, Zhang, Weifang
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container_title International journal of biological sciences
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creator Huang, Yujie
Liu, Ruijuan
Han, Xuechao
Hou, Xiaoyan
Tian, Yonghao
Zhang, Weifang
description 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 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.
doi_str_mv 10.7150/ijbs.63388
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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 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.</description><identifier>ISSN: 1449-2288</identifier><identifier>EISSN: 1449-2288</identifier><identifier>DOI: 10.7150/ijbs.63388</identifier><identifier>PMID: 34975321</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Animals ; Antibodies ; Cancer ; Cell adhesion &amp; migration ; Cell Movement ; Cervical cancer ; Cervix ; Cytoplasm ; Cytoskeleton ; Degradation ; Disease Progression ; Experiments ; Female ; HaCaT Cells ; Health risks ; HeLa Cells ; Human papillomavirus ; Humans ; Infections ; Kinases ; MAP kinase ; Mass spectrometry ; Mass spectroscopy ; Medical prognosis ; Mesenchyme ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 6 - metabolism ; Protein kinase ; Proteins ; rab GTP-Binding Proteins - metabolism ; Research Paper ; Risk analysis ; Risk factors ; Therapeutic targets ; Up-Regulation ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - pathology ; Wound healing ; Xenograft Model Antitumor Assays ; Xenografts ; Xenotransplantation</subject><ispartof>International journal of biological sciences, 2022, Vol.18 (1), p.112-123</ispartof><rights>The author(s).</rights><rights>2022. 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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 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.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>34975321</pmid><doi>10.7150/ijbs.63388</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central
subjects Animals
Antibodies
Cancer
Cell adhesion & migration
Cell Movement
Cervical cancer
Cervix
Cytoplasm
Cytoskeleton
Degradation
Disease Progression
Experiments
Female
HaCaT Cells
Health risks
HeLa Cells
Human papillomavirus
Humans
Infections
Kinases
MAP kinase
Mass spectrometry
Mass spectroscopy
Medical prognosis
Mesenchyme
Metastases
Metastasis
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 6 - metabolism
Protein kinase
Proteins
rab GTP-Binding Proteins - metabolism
Research Paper
Risk analysis
Risk factors
Therapeutic targets
Up-Regulation
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
Wound healing
Xenograft Model Antitumor Assays
Xenografts
Xenotransplantation
title Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation
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