Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
Cancer Sci. 2022 Jun;113(6):2034-2043. doi: 10.1111/cas.15358. Epub 2022 Apr 24.
Ovarian cancer is the fifth most common 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 could 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 show 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.
卵巢癌是女性癌症相关死亡的第五大常见原因。卵巢透明细胞癌(OCCC)是一种化疗耐药的上皮性卵巢癌,预后不良。为了开发能够改善 OCCC 预后的治疗药物,我们使用 CRISPR/Cas9 系统筛选了对 OCCC 肿瘤发生至关重要的蛋白质。在这里,我们显示敲低磷酸盐外排蛋白 XPR1/SLC53A1 可诱导 OCCC 细胞体外生长停滞和凋亡。此外,我们还表明,敲低 XPR1/SLC53A1 可抑制异种移植入免疫缺陷小鼠的 OCCC 细胞的增殖。这些结果表明 XPR1/SLC53A1 在 OCCC 细胞的肿瘤发生中发挥关键作用。我们推测 XPR1/SLC53A1 可能是治疗 OCCC 的有前途的分子靶标。