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.
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Cover Image
Cover Image
Tyrosine (Tyr) phosphorylation has recently emerged as being important for plant receptor kinase (RK)-mediated signalling, particularly during plant immunity. In this issue Mühlenbeck and colleagues (pp. 2759–2774) discuss the current understanding of plant RK Tyr phosphorylation focusing on the critical role of a pTyr site (‘VIa-Tyr’) conserved in several plant RKs. The cover image shows transmembrane signalling mechanisms in choanozoans and plants involving protein kinases. Image courtesy of Cyril Zipfel.
Cancer stem cell phosphatases Available to Purchase
Majid Momeny, Tiina Arsiola, Jukka Westermarck; Cancer stem cell phosphatases. Biochem J 30 July 2021; 478 (14): 2899–2920. doi: https://doi.org/10.1042/BCJ20210254
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