Data from: Downregulation of endometrial mesenchymal marker SUSD2 causes cell senescence and cell death in endometrial carcinoma cells

The cause of death among the majority of endometrial cancer patients involves migration of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into neighbouring organs. It is, thereby, important to identify factors that mediate metastasis. Cell adhesion and migration are modified by the mesenchymal stem cell (MSC) marker Sushi domain containing 2 (SUSD2), a type I transmembrane protein that participates in the orchestration of cell adhesion and migration through interaction with its partner Galactosidase-binding soluble-1 (LGALS1). MSCs have emerged as attractive targets in cancer therapy. Human endometrial adenocarcinoma (Ishikawa) cells were treated with TGFβ (10ng/ml) for 72h. SUSD2, LGALS1 and MKI67 transcript levels were quantified using qRT-PCR. The proportion of SUSD2 positive (SUSD2+) cells and SMAD2/3 abundance were quantified by FACS and Western blotting, respectively. Senescent cells were identified with β-galactosidase staining; cell cycle and cell death were quantified using Propidium Iodide staining. Treatment of endometrial cancer cells (Ishikawa cells) with TGFβ (10ng/ml) significantly decreased SUSD2 transcript levels and the proportion of SUSD2 positive cells. Silencing of SUSD2 using siRNA resulted in senescence and cell death of Ishikawa cells via activation of SMAD2/3. These findings suggest that SUSD2 counteracts senescence and cell death and is thus a potential chemotherapeutic target in human endometrial cancer.绝大多数子宫内膜癌患者的死亡原因，为癌细胞在腹膜腔内发生迁移，随后肿瘤球（cancer spheroids）定植于邻近器官。因此，鉴定介导肿瘤转移的相关因子具有重要研究价值。间充质干细胞（mesenchymal stem cell, MSC）标志物Sushi结构域包含蛋白2（Sushi domain containing 2, SUSD2）可调控细胞黏附与迁移过程：该蛋白属于I型跨膜蛋白，可通过与其配体半乳糖苷酶结合可溶性蛋白1（Galactosidase-binding soluble-1, LGALS1）相互作用，参与调控细胞黏附与迁移。间充质干细胞已成为癌症治疗领域极具潜力的治疗靶点。本研究将人子宫内膜腺癌（Ishikawa）细胞以10ng/ml的转化生长因子β（TGFβ）处理72小时。通过实时定量聚合酶链反应（qRT-PCR）定量检测SUSD2、LGALS1及MKI67的转录水平；分别采用流式细胞术（FACS）与蛋白质免疫印迹（Western blotting）定量分析SUSD2阳性（SUSD2+）细胞比例及SMAD2/3的蛋白丰度；通过β-半乳糖苷酶染色鉴定衰老细胞；采用碘化丙啶（Propidium Iodide）染色定量检测细胞周期与细胞死亡情况。经10ng/ml TGFβ处理的子宫内膜癌细胞（Ishikawa细胞），其SUSD2转录水平及SUSD2阳性细胞比例均显著降低。通过小干扰RNA（siRNA）沉默SUSD2，可通过激活SMAD2/3通路诱导Ishikawa细胞发生衰老并死亡。上述研究结果表明，SUSD2可拮抗细胞衰老与细胞死亡，因此有望成为人子宫内膜癌潜在的化疗靶点。