The E3 ligase RBCK1 reduces the sensitivity of ccRCC to sunitinib through the ANKRD35-MITD1-ANXA1 axis

Wang, Yapeng; Peng, Mou; Zhong, Yawen; Wang, Xiong; Zhu, Liang; Jin, Xin

doi:10.1038/s41388-023-02613-w

Cited by 4 publications

(1 citation statement)

References 34 publications

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“…[15][16][17] In our study, while the expression of LUBAC-mediated linear ubiquitin chains was upregulated in HCC tissues and correlated with poor prognosis of patients with HCC, only HOIL-1, but not HOIP or SHARPIN, was specifically upregulated in HBV-associated HCC and promoted the tumor progression through stabilization of HBX protein. [18] Although studies have shown that LUBAC was also involved in regulating the sensitivity of cancer cells to targeted drugs or chemotherapy in cancers, [15,17,[19][20][21][22] the vital role and underlying mechanisms of LUBAC in regulating the sorafenib resistance and CSC properties in HCC deserve further exploration.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC

Chen,

Dong,

Zhu

et al. 2023

Hepatology

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Background & Aims: Cancer stem cells (CSCs) contribute to therapy resistance in hepatocellular carcinoma (HCC). Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs. Methods: The effect of LUBAC on sorafenib response was evaluated. The role of HOIL-1 in promoting sorafenib resistance and the CSCs properties of HCC were investigated in vitro and in vivo. The mechanism of HOIL-1 in regulating Numb/Notch1 axis was explored using mass spectrometry, co-immunoprecipitation, and western blot. HOIL-1 inhibitors were screened using Autodock Vina, and the anti-tumor effects of pixantrone were evaluated. Results: HOIL-1 contributed to LUBAC-mediated HCC sorafenib resistance independent of its ubiquitin ligase activity. Upregulated HOIL-1 expression enhanced the CSC properties of HCC. Mechanistically, HOIL-1 promoted sorafenib resistance and the CSC properties of HCC via Notch1 signaling. The A64/Q65 residues of HOIL-1 bound with the K78 residue of Numb to impair Numb-mediated Notch1 lysosomal degradation. Notably, pixantrone interrupted HOIL-1/Numb interaction to inhibit Notch1 signaling and CSC properties by targeting the Q65 residue of HOIL-1. Moreover, pixantrone exerted synergistic effects with sorafenib for HCC therapeutic. Conclusion: HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.

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Section: Introductionmentioning

confidence: 99%

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC

Chen,

Dong,

Zhu

et al. 2023

Hepatology

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E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation

Su,

Ding,

Wang

et al. 2024

Free Radical Biology and Medicine

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Sample-specific network analysis identifies gene coexpression patterns of immunotherapy response in advanced kidney cancer

Yin,

Traversa,

Elati

et al. 2024

Preprint

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Immunotherapies have recently emerged as a standard of care for advanced cancers, offering remarkable improvements in patient prognosis. However, only a small proportion of patients respond to the treatment, and no definitive molecular hallmark has been identified for clinical use in predicting treatment outcomes. Here, we propose a sample-specific weighted gene network approach to investigate the heterogeneity of patient clinical outcomes by leveraging multiscale network features derived from gene expression data. Our results on advanced kidney cancer show that patients exhibiting similar clinical benefits share comparable gene coexpression patterns. Increased gene connectivity and stronger negative gene-gene associations are also pivotal factors in patients with poor prognoses. Moreover, integrating pathway genes with topological measures enables the identification of the perturbed regulation of biological pathways associated with treatment responses. Additionally, sample-level network features enhance the prediction performance of gene expression values-based machine learning models. Collectively, our approach provides valuable guidance on the use of gene network information to stratify cancer patients and to optimize treatment strategies.

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The E3 ligase RBCK1 reduces the sensitivity of ccRCC to sunitinib through the ANKRD35-MITD1-ANXA1 axis

Cited by 4 publications

References 34 publications

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC

E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation

Sample-specific network analysis identifies gene coexpression patterns of immunotherapy response in advanced kidney cancer

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