Susd3, or Sushi Domain-Containing 3, is a gene that has shown significance in multiple biological aspects and diseases. It is potentially involved in various biological processes such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway [1]. It has also been associated with estrogen-dependent cell proliferation, cytoskeleton organization, cell-cell and cell-substrate interactions, and migration in breast cancer cells [3].

In breast cancer, studies have demonstrated that SUSD3 is significantly upregulated, and its expression correlates with a favorable prognosis. Clinical correlation analysis shows it is strongly associated with key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification. Univariate and multivariate Cox regression analyses suggest it can be an independent prognostic factor for breast cancer. Drug sensitivity analysis reveals positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. Additionally, in vitro experiments with breast cancer cell lines showed that SUSD3 knockdown significantly reduced cell proliferation and migration [1,2]. In acute myeloid leukemia (AML), SUSD3 was identified as a potential risk factor for prognosis through multiple machine-learning methods [4].

In conclusion, Susd3 plays important roles in biological processes related to cell proliferation, migration, and in disease contexts such as breast cancer and AML. Studies, especially those using in vitro knockdown models (akin to functional loss-of-function models), have provided insights into its role in these diseases, highlighting its potential as a biomarker and therapeutic target in breast cancer and its significance in understanding AML prognosis.

References:

1. Dong, Yan-Ming, Bao, Guo-Qiang. 2024. Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 27, 935-949. doi:10.1007/s12094-024-03641-y. https://pubmed.ncbi.nlm.nih.gov/39107655/

2. Zhong, Fei, Mao, Shining, Peng, Shuangfu, Zhang, Shasha, Wang, Shiyan. 2025. Exploration of SUSD3 in pan-cancer: studying its role, predictive analysis, and biological significance in various malignant tumors in humans. In Frontiers in immunology, 16, 1521965. doi:10.3389/fimmu.2025.1521965. https://pubmed.ncbi.nlm.nih.gov/40191190/

3. Moy, I, Todorović, V, Dubash, A D, Green, K J, Bulun, S E. 2014. Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells. In Oncogene, 34, 323-33. doi:10.1038/onc.2013.553. https://pubmed.ncbi.nlm.nih.gov/24413080/

4. Cheng, Yujing, Yang, Xin, Wang, Ying, Dai, Run, Zhang, Chan. 2024. Multiple machine-learning tools identifying prognostic biomarkers for acute Myeloid Leukemia. In BMC medical informatics and decision making, 24, 2. doi:10.1186/s12911-023-02408-9. https://pubmed.ncbi.nlm.nih.gov/38167056/