title: SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2.
abstract: SOX4, a member of the SOX (sex-determining region Y-related HMG box) transcription factor family, has been reported to be abnormally expressed in a wide variety of cancers, and to exert a pleiotropic function. However, its function in progression of cervical cancer (CC) remains unknown. In this study, we found that SOX4 was highly expressed in CC cells and tissues, and overexpression of SOX4 in CC CaSki cells enhanced tumor clone formation and cell proliferation, and accelerated cell cycle progress. Meanwhile, downregulation of SOX4 by shRNA in CaSki cells inhibited cell proliferation, and slowed cell cycle progress, indicating that SOX4 contributes to the development of CC. In addition, SOX4 overexpression by gene transfer reduced the sensitivity of CaSki cells in response to the chemotherapeutic drug cisplatin, and SOX4 downregulation by RNA interference increased the sensitivity of CaSki cells in response to cisplatin. Moreover, SOX4 overexpression upregulated multiple drug resistant gene ABCG2, and SOX4 downregulation inhibited ABCG2 expression. Taken together, these results suggested that SOX4 functions to modulate cancer proliferation by regulation of cell cycle, and inhibit cancer cell sensitivity to therapeutic drug via upregulation of ABCG2. Thus, SOX4 may be a target for CC chemotherapy.
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, National Health and Family Planning Commission, Changsha, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.|Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: R
authors.initials: R
authors.lastname: Sun
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, National Health and Family Planning Commission, Changsha, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.affiliation: The Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, China.
authors.forename: H
authors.initials: H
authors.lastname: Qi
authors.affiliation: Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, National Health and Family Planning Commission, Changsha, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, National Health and Family Planning Commission, Changsha, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004746:Enoyl-CoA Hydratase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D004746:Enoyl-CoA Hydratase; D002945:Cisplatin