首页|SUB1 promotes colorectal cancer metastasis by activating NF-κB signaling via UBR5-mediated ubiquitination of UBXN1

SUB1 promotes colorectal cancer metastasis by activating NF-κB signaling via UBR5-mediated ubiquitination of UBXN1

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Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(scRNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(Sac-Saccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUBI depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5 mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,pro-viding a new therapeutic strategy for treating metastatic CRC through targeting SUB1.

colorectal cancerMetastasisSUB1UBR5NF-κB signaling

Hao Wang、Wenwen Chen、Yanting Wang、Yuzhen Gao、Zizhen Zhang、Shuyi Mi、Liangjing Wang、Meng Xue

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Department of Gastroenterology,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China

Institution of Gastroenterology,Zhejiang University,Hangzhou 310058,China

Department of Clinical Laboratory,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China

Department of Gastrointestinal Oncology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Peking University Cancer Hospital and Institute,Beijing 100142,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of China

8207322982072623

2024

10.1007/s11427-023-2429-5

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(6)
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