SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2.
SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2.
复制标题
SOX4通过ABCG2促进宫颈癌的进展和对化疗药物的耐药性。
DOI：
10.1038/cddis.2015.290
复制
发表时间：
2015-11-19
影响因子：
9
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Sun R;Jiang B;Qi H;Zhang X;Yang J;Duan J;Li Y;Li G
SOX 4是SOX（sex-determining region Y-related HMG box，性别决定区Y相关HMG盒）转录因子家族的成员，已报道在多种癌症中异常表达，并发挥多效性功能。然而，其在宫颈癌（CC）进展中的作用仍不清楚。在本研究中，我们发现SOX 4在CC细胞和组织中高表达，并且SOX 4在CC CaSki细胞中的过表达促进肿瘤克隆形成和细胞增殖，并加速细胞周期进程。同时，在CaSki细胞中下调SOX 4表达可抑制细胞增殖，延缓细胞周期进程，提示SOX 4参与了CC的发生发展。此外，通过基因转移的SOX 4过表达降低了CaSki细胞对化疗药物顺铂的敏感性，而通过RNA干扰的SOX 4下调增加了CaSki细胞对顺铂的敏感性。SOX 4过表达上调多药耐药基因ABCG 2的表达，而SOX 4下调则抑制ABCG 2的表达。综上所述，这些结果表明，SOX 4通过调节细胞周期来调节癌症增殖，并通过上调ABCG 2来抑制癌细胞对治疗药物的敏感性。因此，SOX 4可能是CC化疗的靶点。
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.