Department of Physiology, University of Louisville, 505 South Hancock Street, Clinical and Translational Research Building, Room 322, Louisville, KY, 40202, USA.
James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Stem Cell Rev Rep. 2019 Dec;15(6):866-879. doi: 10.1007/s12015-019-09911-5.
Origin of cancer stem cells (CSCs) and mechanisms by which oncogene PTTG1 contributes to tumor progression via CSCs is not known. Ovarian CSCs exhibit characteristics of self-renewal, tumor-initiation, growth, differentiation, drug resistance, and tumor relapse. A common location of putative origin, namely the ovarian surface epithelium, is shared between the normal stem and CSC compartments. Existence of ovarian stem cells and their co-expression with CSC signatures suggests a strong correlation between origin of epithelial cancer and CSCs. We hereby explored a putative oncogene PTTG1 (Securin), reported to be overexpressed in various tumors, including ovarian. We report a previously overlooked role of PTTG1 as a marker of CSCs thereby modulating CSC, germline, and stemness-related genes. We further characterized PTTG1's ability to regulate (cancer) stem cell-associated self-renewal and epithelial-mesenchymal transition pathways. Collectively, the data sheds light on a potential target expressed during ovarian tumorigenesis and metastatically disseminated ascites CSCs in the peritoneal cavity. Present study highlights this unconventional, under-explored role of PTTG1 in regulation of stem and CSC compartments in ovary, ovarian cancer and ascites and highlights it as a potential candidate for developing CSC specific targeted therapeutics.
癌症干细胞 (CSCs) 的起源以及癌基因 PTTG1 通过 CSCs 促进肿瘤进展的机制尚不清楚。卵巢 CSCs 表现出自我更新、肿瘤起始、生长、分化、耐药和肿瘤复发的特征。正常干细胞和 CSC 区室之间存在一个共同的假定起源部位，即卵巢表面上皮。卵巢干细胞的存在及其与 CSC 特征的共表达表明上皮性癌症的起源与 CSCs 之间存在很强的相关性。我们在此探讨了一种假定的癌基因 PTTG1（Securin），据报道它在多种肿瘤中过度表达，包括卵巢癌。我们报告了 PTTG1 作为 CSCs 标志物的先前被忽视的作用，从而调节 CSC、生殖细胞和干性相关基因。我们进一步表征了 PTTG1 调节（癌症）干细胞相关自我更新和上皮-间充质转化途径的能力。总的来说，这些数据揭示了在卵巢肿瘤发生和腹腔中转移性播散性腹水 CSCs 中表达的一个潜在靶点。本研究强调了 PTTG1 在卵巢、卵巢癌和腹水的干细胞和 CSC 区室调节中的这种非常规、探索不足的作用，并强调它可能是开发 CSC 特异性靶向治疗的潜在候选者。
