SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2

Cell Death Dis. 2015 Nov 19;6(11):e1990. doi: 10.1038/cddis.2015.290.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Cycle / physiology
  • Cell Proliferation / physiology
  • Cisplatin / pharmacology
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Enoyl-CoA Hydratase / genetics
  • Enoyl-CoA Hydratase / metabolism
  • Female
  • HeLa Cells
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism*
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Enoyl-CoA Hydratase
  • Cisplatin