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.

lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer

“…Sox4, the member of the Sox (Sry-related high mobility group box) family of transcription factors, is as a master mediator in tumorigenicity and cancer stemness (33). Sox4 is upregulated in various cancers, such as colorectal, prostate cancer and EC (34)(35)(36). The expression of Sox4 was posttranscriptionally regulated by miR-363, miR-204 and miR-187 (23,37,38).…”

SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

“…Accumulating evidence has indicated that SOX genes play an important role in drug resistance and CSCs or EMT. For example, SOX4 is a tumor promoter that contributes to drug resistance and progression in cervical cancer and regulates the EMT programme in breast cancer . More interestingly, SOX4 is also highly expressed during metastasis and is specifically associated with lymph node metastasis in TSCC .…”

“…For example, SOX4 is a tumor promoter that contributes to drug resistance and progression in cervical cancer and regulates the EMT programme in breast cancer. 10,11 More interestingly, SOX4 is also highly expressed during metastasis and is specifically associated with lymph node metastasis in TSCC. 12 Conversely, the overexpression of SOX9 promotes self-renewal properties and in vivo tumorigenicity by facilitating symmetrical cell division in liver cancer.…”

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

“…Consistent with an oncogenic role, some studies found that transduction of CC cell lines with SOX2 , SOX4 , and SOX18 promoted cell proliferation, metastasis, and invasion 52,66-68 . Specifically, endogenous overexpression of SOX2 or SOX4 in CC cell lines drove the cell cycle from G0/G1 to S stage by promoting expression of cell cycle promoters, such as cyclinE2, minichromosome maintenance protein 10 (MCM10), and weel protein kinase 52,66 . Overexpression of SOX2 in CC cell lines also promoted metastasis and invasion by augmenting the expression of epithelial–mesenchymal transition-promoted molecules, such as vimentin, β-catenin, and Snail 67 .…”

“…Superficially, expression level of SOX2 was higher in tissues from patients with radiation-resistance compared with those with radiation-sensitivity, suggesting that SOX2 was a biomarker of unfavorable therapeutic reactivity 51 . Overexpression of SOX genes, such as SOX4 , in Caski cell lines also decreased the treatment efficacy of cisplatin by up-regulating the drug efflux transporter gene ABCG2 52 . And more investigations are required to explore how SOX genes influence treatment efficacy in patients with CC.…”