Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Cancer Sci. 2019 May;110(5):1804-1813. doi: 10.1111/cas.14007. Epub 2019 Apr 11.
Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. We reported previously that aldehyde dehydrogenase 1 (ALDH1), a predominant isoform of the ALDH family in mammals and a potential marker of normal and malignant stem cells, is related to the tumorigenic potential of EC. We compared the levels of various proteins in human EC cells with high and low ALDH1 expression using shotgun proteomics and found that serum deprivation-response protein (SDPR) was preferentially expressed in cells with high ALDH1 expression. Also known as cavin-2, SDPR is a member of the cavin protein family, which is required for the formation of caveolae. Using SDPR-knockout EC cells generated using the CRISPR/Cas9 system, we revealed that SDPR was correlated with invasion, migration, epithelial-mesenchymal transition, and colony formation, as well as the expression of ALDH1. RNA sequencing showed that integrin-linked kinase (ILK) signaling is involved in the effect of SDPR on ALDH1. Immunohistochemical analysis revealed that the localization of ILK at the cell cortex was disrupted by SDPR knockout, potentially interfering with ILK signaling. Moreover, immunohistochemical analysis of clinical samples showed that SDPR is related to histological characteristics associated with invasiveness, such as poor differentiation, lymphatic invasion, and the microcystic, elongated, and fragmented histopathological pattern. This is, to our knowledge, the first report that SDPR is related to tumor progression.
子宫内膜样癌（EC）是女性生殖系统最常见的恶性肿瘤之一。我们之前报道过，醛脱氢酶 1（ALDH1）是哺乳动物 ALDH 家族的主要亚型，也是正常和恶性干细胞的潜在标志物，与 EC 的致瘤潜能有关。我们使用鸟枪法蛋白质组学比较了高表达和低表达 ALDH1 的人 EC 细胞中的各种蛋白质水平，发现血清剥夺反应蛋白（SDPR）在高 ALDH1 表达的细胞中优先表达。SDPR 也称为 cavin-2，是 cavin 蛋白家族的成员，该蛋白家族对于形成 caveolae 是必需的。使用 CRISPR/Cas9 系统生成的 SDPR 敲除 EC 细胞，我们揭示了 SDPR 与侵袭、迁移、上皮间质转化和集落形成以及 ALDH1 的表达相关。RNA 测序显示，整合素连接激酶（ILK）信号参与了 SDPR 对 ALDH1 的影响。免疫组织化学分析显示，SDPR 敲除破坏了细胞皮质处的 ILK 定位，可能干扰了 ILK 信号。此外，临床样本的免疫组织化学分析表明，SDPR 与与侵袭性相关的组织学特征有关，如分化不良、淋巴管浸润以及微囊状、拉长和碎片化的组织病理学模式。这是我们所知的第一个表明 SDPR 与肿瘤进展有关的报告。
