STAMBPL1, also known as STAM binding protein-like 1, is a Lys-63 linkage-specific deubiquitinase [2]. It plays crucial roles in multiple cellular processes by regulating the ubiquitination status of various proteins, thereby influencing associated pathways such as mTOR, EGFR-related, Wnt/β-catenin, and NF-κB signaling pathways. Its functions are significant in maintaining normal cell metabolism, growth, and survival, and it is closely related to cancer development [1,2,5]. Genetic models, like knockout models, are valuable for studying STAMBPL1's functions.

Knockout of STAMBPL1 in a human colon cancer cell line suppresses xenograft tumor growth, indicating its role in promoting cancer progression through modulating mTORC1 signaling as it controls the polyubiquitination level of Sestrin2 in response to leucine availability [1]. In hepatocellular carcinoma, STAMBPL1 deficiency attenuates liver tumorigenesis in vitro and in vivo. It modulates the stability of EGFR protein and mRNA, and the EGFR-MYC axis has a positive feedback regulation on its transcription [2]. In lung adenocarcinoma, knockdown of STAMBPL1 in A549 and H1299 cells suppresses cell growth, migration, evasiveness, colony-forming ability, and promotes apoptosis, suggesting its role in tumor progression by inhibiting DHRS2 expression [3]. In kidney renal clear cell carcinoma, silencing STAMBPL1 can decrease the mesenchymal phenotype and enhance the antitumor effects of PD-1 blockade and tyrosine kinase inhibitor sunitinib [4]. In breast cancer, depletion of STAMBPL1 sensitizes breast cancer cells to cisplatin in vitro and in vivo [6]. In gastric cancer, STAMBPL1 knockdown suppresses cell proliferation, increases apoptosis, and reduces invasion and migration [7].

In conclusion, STAMBPL1, as a deubiquitinase, has essential functions in regulating multiple signaling pathways. Model-based research, especially knockout studies, reveals its significant role in various cancer types, including colon, liver, lung, kidney, breast, and gastric cancers. Understanding STAMBPL1 can provide potential therapeutic targets for cancer treatment.

References:

1. Wang, Dong, Xu, Chenchen, Yang, Wenyu, Guan, Jialiang, Liu, Ying. 2022. E3 ligase RNF167 and deubiquitinase STAMBPL1 modulate mTOR and cancer progression. In Molecular cell, 82, 770-784.e9. doi:10.1016/j.molcel.2022.01.002. https://pubmed.ncbi.nlm.nih.gov/35114100/

2. Zhang, Hongli, Wang, Zixuan, Zhang, Jian, Chen, Wei-Dong, Wang, Yan-Dong. 2024. A MYC-STAMBPL1-TOE1 positive feedback loop mediates EGFR stability in hepatocellular carcinoma. In Cell reports, 43, 114812. doi:10.1016/j.celrep.2024.114812. https://pubmed.ncbi.nlm.nih.gov/39388352/

3. Yang, Xiang, Ling, Liqun, Li, Changhong, Wang, Yumin, Hu, Lijuan. 2023. STAMBPL1 promotes the progression of lung adenocarcinoma by inhibiting DHRS2 expression. In Translational oncology, 35, 101728. doi:10.1016/j.tranon.2023.101728. https://pubmed.ncbi.nlm.nih.gov/37393834/

4. Huang, Shiyu, Qin, Xuke, Fu, Shujie, Chen, Zhiyuan, Wang, Lei. 2024. STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2405083. doi:10.1002/advs.202405083. https://pubmed.ncbi.nlm.nih.gov/39527690/

5. Jin, Junyi, Wang, Yihui, Hu, Yaoyuan. 2024. STAMBPL1, transcriptionally regulated by SREBP1, promotes malignant behaviors of hepatocellular carcinoma cells via Wnt/β-catenin signaling pathway. In Molecular carcinogenesis, 63, 2158-2173. doi:10.1002/mc.23801. https://pubmed.ncbi.nlm.nih.gov/39150093/

6. Liu, Rong, Yang, Guangxi, Bao, Min, Huang, Jian, Chen, Ceshi. 2022. STAMBPL1 promotes breast cancer cell resistance to cisplatin partially by stabilizing MKP-1 expression. In Oncogene, 41, 2265-2274. doi:10.1038/s41388-022-02252-7. https://pubmed.ncbi.nlm.nih.gov/35236965/

7. Yu, Da-Jun, Qian, Jun, Jin, Xin, Guo, Chen-Xu, Yue, Xi-Cheng. 2019. STAMBPL1 knockdown has antitumour effects on gastric cancer biological activities. In Oncology letters, 18, 4421-4428. doi:10.3892/ol.2019.10789. https://pubmed.ncbi.nlm.nih.gov/31611951/