2. Academic Validation
  3. ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling

ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling

  • Cell Death Differ. 2024 Jan 16. doi: 10.1038/s41418-024-01256-y.
Ying He # 1 2,  Qian Shi # 1 2,  Yuhang Ling 1 2,  Huihui Guo 1 2,  Yi Fei 3,  Ruoyu Wu 4,  Chengwu Tang 5 6,  Xilin Zhang 7 8,  Linhua Yao 9 10
Affiliations

Affiliations

  • 1 Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China.
  • 2 Huzhou Key Laboratory of Translational Medicine, First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang, China.
  • 3 Department of Colorectal Surgery, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China.
  • 4 Department of Gastroenterology, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China.
  • 5 Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China. tamgche@sina.com.
  • 6 Huzhou Key Laboratory of Translational Medicine, First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang, China. tamgche@sina.com.
  • 7 Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China. 51378@zjhu.edu.cn.
  • 8 Huzhou Key Laboratory of Translational Medicine, First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang, China. 51378@zjhu.edu.cn.
  • 9 Huzhou Key Laboratory of Translational Medicine, First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang, China. yaolinhua110@163.com.
  • 10 Department of Gastroenterology, First Affiliated Hospital of Huzhou University, Huzhou, 313000, Zhejiang, China. yaolinhua110@163.com.
  • # Contributed equally.
PMID: 38228802 DOI: 10.1038/s41418-024-01256-y
Abstract

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, has been reported as a suppressor in several tumors whereas its role in colorectal Cancer (CRC) remains unknown. In this study, we find that ABLIM1 is up-regulated in CRC patients and high levels of ABLIM1 predict short disease-free survival time. Knock-down of ABLIM1 in CRC cell lines by lenti-virus leads to inhibited cell proliferation, migration, and invasion capabilities in vitro and impaired growth of tumor xenografts and liver metastasis lesions in vivo, while ABLIM1 overexpression accelerates tumor growth and invasion in vitro. Mechanistically, we uncover that ABLIM1 activates the NF-ĸB/CCL-20 signaling through modulating IĸBα ubiquitination and proteasomal-mediated degradation. Further co-immunoprecipitation, in vivo and in vitro ubiquitination assays reveal ABLIM1 as a novel ubiquitin E3 ligase binding to IĸBα. Interestingly, The E3 ligase catalysis activity of ABLIM1 depends on its 402-778aa rather than its LIM domains and its interaction with IĸBα relies on the HP domain. Our findings delineate the oncogenic role of ABLIM1 in CRC progression and reveal it as a novel E3 ligase targeting IĸBα, providing new insights into the regulation of NF-ĸB signaling in tumors.

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