Shcbp1-KO Mouse

Shcbp1, or Shc SH2-domain binding protein 1, is a protein that specifically binds to the SH2 domain of Src homolog and collagen homolog (Shc). It participates in the regulation of multiple signal transduction pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-β1/Smad and β -catenin signaling. Shcbp1 is involved in T cell development, regulation of downstream signal transduction, and cytokinesis during mitosis and meiosis, and thus is of great biological importance [1]. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In transgenic mice, Shcbp1 knockout significantly hindered tumor progression and metastasis in ductal carcinomas, prolonging survival. Single-cell transcriptome analysis showed that SHCBP1 deficiency was functionally linked to increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant and centrosome, suggesting that the inhibition of tumor progression by SHCBP1 loss depended on the recovery of ciliogenesis [2]. In addition, knockout of SHCBP1 in pancreatic cancer inhibited the proliferation and migration of PC cells in vitro, and suppressed tumor growth in vivo [3].

In conclusion, Shcbp1 plays a crucial role in multiple biological processes including signal transduction and cell division. The use of Shcbp1 KO mouse models has revealed its significance in tumor-related processes, especially in ductal carcinomas and pancreatic cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Zhang, Geng-Yuan, Ma, Zhi-Jian, Wang, Long, Shi, Wen-Gui, Jiao, Zuo-Yi. . The Role of Shcbp1 in Signaling and Disease. In Current cancer drug targets, 19, 854-862. doi:10.2174/1568009619666190620114928. https://pubmed.ncbi.nlm.nih.gov/31250756/

2. Shi, Wengui, Li, Lianshun, Zhao, Huiming, Yu, Zeyuan, Jiao, Zuoyi. . Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma. In Cancer research, 84, 4156-4172. doi:10.1158/0008-5472.CAN-24-1095. https://pubmed.ncbi.nlm.nih.gov/39312205/

3. Ma, Zhijian, Gu, Qianlin, Dai, Yiwei, Shi, Wengui, Jiao, Zuoyi. 2023. Therapeutic potential of SHCBP1 inhibitor AZD5582 in pancreatic cancer treatment. In Cancer science, 115, 820-835. doi:10.1111/cas.16059. https://pubmed.ncbi.nlm.nih.gov/38151993/