FBW7 in hematological tumors (Review)

Zhu, Qiaojuan; Hu, Linjun; Guo, Yang; Xiao, Zunqiang; Xu, Qiuran; Tong, Xiangmin

doi:10.3892/ol.2020.11264

Cited by 11 publications

(12 citation statements)

References 83 publications

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“…It is involved in the ubiquitination and degradation of many oncogenes and transcription factors, including p53, c-Myc, c-Jun, HSF1, NF-kB and Notch. Accumulating evidence reveals that the abnormal expression of FBW7 is involved in the development of hematological cancers [ 35 ]. T-cell acute lymphoblastic leukemia (T-ALL) is the only hematological tumor that can be caused by the deletion of FBXW7 without the necessity of other cancer-promoting elements [ 36 ].…”

Section: Deregulation Of Ups In Hematological Malignanciesmentioning

confidence: 99%

The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options

Costanzo

Gaudio

Conte

et al. 2020

Cancers

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The ubiquitin proteasome system (UPS) is the main cellular degradation machinery designed for controlling turnover of critical proteins involved in cancer pathogenesis, including hematological malignancies. UPS plays a functional role in regulating turnover of key proteins involved in cell cycle arrest, apoptosis and terminal differentiation. When deregulated, it leads to several disorders, including cancer. Several studies indicate that, in some subtypes of human hematological neoplasms such as multiple myeloma and Burkitt’s lymphoma, abnormalities in the UPS made it an attractive therapeutic target due to pro-cancer activity. In this review, we discuss the aberrant role of UPS evaluating its impact in hematological malignancies. Finally, we also review the most promising therapeutic approaches to target UPS as powerful strategies to improve treatment of blood cancers.

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Section: Deregulation Of Ups In Hematological Malignanciesmentioning

confidence: 99%

The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options

Costanzo

Gaudio

Conte

et al. 2020

Cancers

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“…FBXW7 is one of the F-box proteins, which acts as a tumor suppressor through ubiquitination and inducing the degradation of numerous important transcription factors and proto-onco proteins in numerous human cancer, including leukemia [ 65 ]. Based on the Oncomine database ( , accessed on 5 January 2020), FBXW7 expression is reported to be higher in leukemia than in other malignancies and normal tissues [ 65 ]. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase that is overexpressed in cancers (including AML), where it promotes self-renewal, growth, and survival of malignant cells [ 66 ].…”

Section: Ubiquitination In Amlmentioning

confidence: 99%

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Park

Baek

2022

IJMS

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Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

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“…In addition to Notch1, a similar pattern of mutations occurs at other Notch genes in several types of hematological malignancies and solid tumors, such as chronic lymphocytic leukemia (CLL) [76], B-cell malignancies [77][78][79][80], triple-negative breast cancer (TNBC) [81], adenoid cystic carcinoma (ACC) [82], and non-small-cell lung cancer (NSCLC) [83]. Moreover, hyper-activated Notch has been related to missense mutations at the FBXW7 coding sequence in several hematological malignancies, including approximately 30% of T-ALL patients [84]. Mechanistically, loss-of-function mutations in the FBXW7 gene, by preventing the FBXW7-mediated NIC degradation, extend its half-life and amplify the output of the signal.…”

Section: Mechanisms Of Notch Signaling Alteration In Cancermentioning

confidence: 99%

Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives

Zhdanovskaya

Firrincieli

Lazzari

et al. 2021

Cancers

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Notch signaling guides cell fate decisions by affecting proliferation, apoptosis, stem cell self-renewal, and differentiation depending on cell and tissue context. Given its multifaceted function during tissue development, both overactivation and loss of Notch signaling have been linked to tumorigenesis in ways that are either oncogenic or oncosuppressive, but always context-dependent. Notch signaling is critical for several mechanisms of chemoresistance including cancer stem cell maintenance, epithelial-mesenchymal transition, tumor-stroma interaction, and malignant neovascularization that makes its targeting an appealing strategy against tumor growth and recurrence. During the last decades, numerous Notch-interfering agents have been developed, and the abundant preclinical evidence has been transformed in orphan drug approval for few rare diseases. However, the majority of Notch-dependent malignancies remain untargeted, even if the application of Notch inhibitors alone or in combination with common chemotherapeutic drugs is being evaluated in clinical trials. The modest clinical success of current Notch-targeting strategies is mostly due to their limited efficacy and severe on-target toxicity in Notch-controlled healthy tissues. Here, we review the available preclinical and clinical evidence on combinatorial treatment between different Notch signaling inhibitors and existent chemotherapeutic drugs, providing a comprehensive picture of molecular mechanisms explaining the potential or lacking success of these combinations.

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FBW7 in hematological tumors (Review)

Cited by 11 publications

References 83 publications

The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options

The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives

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