Huang Yake, Huang Jiani, Huang Yan, Gan Lei, Long Ling, Pu Aimin, Xie Rongkai
Department of Obstetrics and Gynecology, Xinqiao Hospital, Army Medical University Chongqing 400037, China.
Institute of Cancer, Xinqiao Hospital, Army Medical University Chongqing 400037, China.
Am J Cancer Res. 2020 Jan 1;10(1):131-147. eCollection 2020.
Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer death. Recent studies have reported that iron overload could accelerate cancer progression. TFRC is an important participant in intracellular iron transport, and we noticed that it was abnormally overexpressed in EOC; however, its specific role in EOC remained unclear. Therefore, our study aimed to reveal the clinical significance and biological function of TFRC in human EOC. First, we detected dramatically increased TFRC expression in EOC tissues, which was associated with a worse prognosis for patients. Subsequently, we verified that TFRC knockdown significantly inhibited the proliferation and metastasis of EOC cells (SKOV3 and A2780) and . More significantly, we demonstrated that TFRC-mediated proliferation and metastasis of EOC cells resulted from its positive regulation of AXIN2 expression. In conclusion, our findings suggest that TFRC accelerates the progression of EOC by promoting cancer cell proliferation and metastasis via upregulation of AXIN2 expression, which highlights its potential as a novel therapeutic target for human EOC.
上皮性卵巢癌(EOC)是妇科癌症死亡的最常见原因。最近的研究报告称,铁过载会加速癌症进展。转铁蛋白受体(TFRC)是细胞内铁转运的重要参与者,我们注意到它在EOC中异常过度表达;然而,其在EOC中的具体作用仍不清楚。因此,我们的研究旨在揭示TFRC在人类EOC中的临床意义和生物学功能。首先,我们检测到EOC组织中TFRC表达显著增加,这与患者预后较差有关。随后,我们证实TFRC敲低显著抑制了EOC细胞(SKOV3和A2780)的增殖和转移。更重要的是,我们证明TFRC介导的EOC细胞增殖和转移是由于其对AXIN2表达的正向调节。总之,我们的研究结果表明,TFRC通过上调AXIN2表达促进癌细胞增殖和转移,从而加速EOC的进展,这突出了其作为人类EOC新型治疗靶点的潜力。