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J Cancer 2024; 15(7):1870-1879. doi:10.7150/jca.92723 This issue Cite

Research Paper

TRIM67 Promotes Non-Small Cell Lung Cancer Development by Positively Regulating the Notch Pathway through DLK1 Ubiquitination

Jun Jiang, Xinjie Dong, Jixuan Liu, Ting Liu, Xiaoshuai Chen, Xiaolei Bian, Ming Li, Yafang Liu^✉

Department of Pathology, Lequn Branch, The First Hospital of Jilin University, Changchun, China.

✉ Corresponding author: Tel: +86 17767727811; Fax: +86 84886631; Email: yafangliuedu.cn; Address: Department of Pathology, Lequn Branch, The First Hospital of Jilin University, No. 3302 Jilin Road, Jilin, Changchun 130000, China.

Abstract

Tripartite motif-containing 67 (TRIM67), a member of the TRIM protein family, is an E3 ubiquitin ligase. Our previous study revealed a relationship between TRIM67 expression and carcinogenesis, showing that TRIM67 expression is linked to p-TNM stage, lymph node metastasis, tumour size, cancer cell differentiation, and poor prognosis. Additionally, TRIM67 immunostaining results were associated with clinicopathological features. TRIM67 activated the Notch pathway in a favourable manner to enhance cell invasion, migration, and proliferation. Atypical ligand delta like non-canonical Notch ligand 1 (DLK1) inhibits the function of the Notch1 receptor, which in turn prevents activation of the Notch pathway. In addition, we investigated the mechanism by which TRIM67 influences the Notch pathway. We found that TRIM67 altered the behaviour of non-small cell lung cancer (NSCLC) cells by ubiquitinating DLK1 via its RING domain, which in turn activates the Notch pathway. Taken together, these findings indicate that TRIM67 may be involved in promoting the growth of NSCLC.

Keywords: DLK1, non-small cell lung cancer, Notch, TRIM67

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