The phosphate exporter XPR1/SLC53A1 is required for the tumorigenicity of ovarian cancer.

Ovarian cancer is the fifth cause of cancer-related death in women. Ovarian clear cell carcinoma (OCCC) is a chemotherapy-resistant epithelial ovarian cancer with poor prognosis. As a basis for the development of therapeutic agents that may improve the prognosis of OCCC, we performed a screen for proteins critical for the tumorigenicity of OCCC using the CRISPR/Cas9 system. Here we show that knockdown of the phosphate exporter XPR1/SLC53A1 induces the growth arrest and apoptosis of OCCC cells in vitro. Moreover, we demonstrate that knockdown of XPR1/SLC53A1 inhibits the proliferation of OCCC cells xenografted into immunocompromised mice. These results suggest that XPR1/SLC53A1 plays a critical role in the tumorigenesis of OCCC cells. We speculate that XPR1/SLC53A1 might be a promising molecular target for the therapeutic treatment of OCCC. RNA profiles of ovarian cancer cells (OVISE, TOV21G, ES2, JHOC5) treated with control (Mock, siNC#1, siNC#2; n = 3) or XPR1 siRNA (siXPR1#1~#3; n = 3).

卵巢癌是女性癌症相关死亡的第五大病因。卵巢透明细胞癌（Ovarian clear cell carcinoma, OCCC）是一类化疗耐药性上皮性卵巢癌，预后较差。为研发可改善OCCC患者预后的治疗药物，我们利用CRISPR/Cas9系统开展了OCCC致瘤关键蛋白的筛选实验。本研究结果显示，敲低磷酸盐输出蛋白XPR1/SLC53A1可在体外诱导OCCC细胞发生生长停滞与凋亡。此外，我们还证实，敲低XPR1/SLC53A1能够抑制异种移植于免疫缺陷小鼠体内的OCCC细胞增殖。上述结果表明，XPR1/SLC53A1在OCCC细胞的肿瘤发生过程中发挥关键调控作用。我们推测，XPR1/SLC53A1有望成为OCCC临床治疗的潜在分子靶点。本数据集包含经对照处理（Mock、siNC#1、siNC#2，每组n=3）或XPR1小干扰RNA（siXPR1#1~#3，每组n=3）处理的卵巢癌细胞系（OVISE、TOV21G、ES2、JHOC5）的RNA转录谱数据。