Cancer stem cells (CSCs) are involved in the initiation and progression of human malignancies by enabling cancer tissue self-renewal capacity and constituting the therapy-resistant population of tumor cells. However, despite the exhausting characterization of CSC genetics, epigenetics, and kinase signaling, eradication of CSCs remains an unattainable goal in most human malignancies. While phosphatases contribute equally with kinases to cellular phosphoregulation, our understanding of phosphatases in CSCs lags severely behind our knowledge about other CSC signaling mechanisms. Many cancer-relevant phosphatases have recently become druggable, indicating that further understanding of the CSC phosphatases might provide novel therapeutic opportunities. This review summarizes the current knowledge about fundamental, but yet poorly understood involvement of phosphatases in the regulation of major CSC signaling pathways. We also review the functional roles of phosphatases in CSC self-renewal, cancer progression, and therapy resistance; focusing particularly on hematological cancers and glioblastoma. We further discuss the small molecule targeting of CSC phosphatases and their therapeutic potential in cancer combination therapies.

中文翻译：

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癌症干细胞磷酸酶

癌症干细胞 (CSC) 通过使癌症组织具有自我更新能力并构成抗治疗的肿瘤细胞群，参与了人类恶性肿瘤的发生和发展。然而，尽管对 CSC 遗传学、表观遗传学和激酶信号传导进行了详尽的表征，但在大多数人类恶性肿瘤中，根除 CSCs 仍然是一个无法实现的目标。虽然磷酸酶与激酶对细胞磷酸调节的贡献相同，但我们对 CSC 中磷酸酶的理解严重落后于我们对其他 CSC 信号传导机制的了解。许多与癌症相关的磷酸酶最近变得可药化，表明进一步了解 CSC 磷酸酶可能提供新的治疗机会。这篇综述总结了当前关于基本面、但对磷酸酶在调节主要 CSC 信号通路中的作用知之甚少。我们还回顾了磷酸酶在 CSC 自我更新、癌症进展和治疗抵抗中的功能作用；特别关注血液癌症和胶质母细胞瘤。我们进一步讨论了 CSC 磷酸酶的小分子靶向及其在癌症联合疗法中的治疗潜力。