SAMMSON drives the self-renewal of liver tumor initiating cells through EZH2-dependent Wnt/β-catenin activation
نویسندگان
چکیده
Liver cancer is one of the most serious cancers all over the world. Liver tumor initiating cells (TICs) account for tumor initiation and metastasis. However, the regulatory mechanism of liver TICs remains unclear. Here we found long noncoding RNA SAMMSON is highly expressed in liver cancer and liver TICs. SAMMSON silenced cells show impaired self-renewal capacity, while, its overexpression induces enhanced self-renewal. SAMMSON drives the activation of Wnt/β-catenin signaling, and thus promotes liver TIC self-renewal. SAMMSON interacts with EZH2, a core component of PRC2 complex, and inhibits the expression of CTNNBIP1 through EZH2 dependent manner. SAMMSON binds to CTNNBIP1 promoter and recruits EZH2 to CTNNBIP1 promoter. What's more, targeting liver TICs through SAMMSON, EZH2 and Wnt/β-catenin signaling impaired liver TIC self-renewal, decreased tumor propagation and severity. Taken together, SAMMSON drives liver TIC self-renewal through EZH2-dependent Wnt/β-catenin activation.
منابع مشابه
EZH2 promotes colorectal cancer stem-like cell expansion by activating p21cip1-Wnt/β-catenin signaling
Because colorectal cancer (CRC) stem-like cells (CCS-like cells) contribute to poor patient prognosis, these cells are a potential target for CRC therapy. However, the mechanism underlying the maintenance of CCS-like cell properties remains unclear. Here, we found that patients with advanced stage CRC expressed high levels of polycomb group protein enhancer of zeste homologue 2 (EZH2). High exp...
متن کاملCWP232228 targets liver cancer stem cells through Wnt/β-catenin signaling: a novel therapeutic approach for liver cancer treatment
Liver cancer stem cells (CSCs) are resistant to conventional chemotherapy and radiation, which may destroy tumor masses, but not all liver CSCs contribute to tumor initiation, metastasis, and relapse. In the present study, we showed that liver CSCs with elevated Wnt/β-catenin signaling possess much greater self-renewal and clonogenic potential. We further documented that the increased clonogeni...
متن کاملGlycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma.
Embryonal rhabdomyosarcoma (ERMS) is a common pediatric malignancy of muscle, with relapse being the major clinical challenge. Self-renewing tumor-propagating cells (TPCs) drive cancer relapse and are confined to a molecularly definable subset of ERMS cells. To identify drugs that suppress ERMS self-renewal and induce differentiation of TPCs, a large-scale chemical screen was completed. Glycoge...
متن کاملA Regulatory Network Involving β‐Catenin, e‐Cadherin, PI3k/Akt, and Slug Balances Self‐Renewal and Differentiation of Human Pluripotent Stem Cells In Response to Wnt Signaling
The mechanisms underlying disparate roles of the canonical Wnt signaling pathway in maintaining self-renewal or inducing differentiation and lineage specification in embryonic stem cells (ESCs) are not clear. In this study, we provide the first demonstration that self-renewal versus differentiation of human ESCs (hESCs) in response to Wnt signaling is predominantly determined by a two-layer reg...
متن کاملAURKA governs self-renewal capacity in glioma-initiating cells via stabilization/activation of β-catenin/Wnt signaling.
UNLABELLED Glioma-initiating cells (GIC), which are characterized by their self-renewal capacity and tumorigenicity, were recently identified as a highly tumorigenic subpopulation of glioblastoma multiforme and are considered responsible for glioblastoma recurrence and chemo/radiation resistance. Previously, it was revealed that Wnt signaling activation is critical to the self-renewal of GICs. ...
متن کامل