Stat5a, short for Signal Transducer and Activator of Transcription 5A, is a transcription factor that mediates signals for numerous cytokines. It is involved in key cellular functions such as proliferation, differentiation, and apoptosis, playing significant roles in hematopoiesis, immunoregulation, and cancer-related pathways [1,2,3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In hematopoiesis, although Stat5a and Stat5b were once thought to have redundant roles, recent evidence highlights differences, with Stat5b having a more prominent role in normal and malignant hematopoiesis [1]. In gastric cancer, increased p-Stat5a levels are linked to tumor invasion and poor prognosis, and Stat5a promotes cancer cell proliferation by upregulating CD44 expression [2]. In prostate cancer, PAX6 drives neuroendocrine phenotypes through the MET/Stat5a signaling pathway [3]. In chondrocytes, Stat5a promotes Col10a1 gene expression and hypertrophic differentiation [4]. In diabetic nephropathy, Stat5a participates in high-glucose-mediated endothelial-to-mesenchymal transition (EndMT) by regulating ELTD1 transcription [5]. In atherosclerosis, GM-CSF-activated Stat5a regulates macrophage functions and inflammation [6]. In breast cancer, Stat5a confers doxorubicin resistance by regulating ABCB1 [7]. Also, studies on STAT5a expression across cancer types show it has different prognostic roles depending on the cancer type [8].

In summary, Stat5a is crucial for various biological processes and diseases. Model-based research, especially KO/CKO mouse models, has revealed its diverse functions in areas like hematopoiesis, multiple cancers, diabetic nephropathy, and atherosclerosis, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Maurer, Barbara, Kollmann, Sebastian, Pickem, Judith, Hoelbl-Kovacic, Andrea, Sexl, Veronika. 2019. STAT5A and STAT5B-Twins with Different Personalities in Hematopoiesis and Leukemia. In Cancers, 11, . doi:10.3390/cancers11111726. https://pubmed.ncbi.nlm.nih.gov/31690038/

2. Wang, Shanglin, Fan, Rong, Gao, Huayu, Wang, Yunshan, Jia, Yanfei. 2023. STAT5A modulates gastric cancer progression via upregulation of CD44. In Genomics, 115, 110638. doi:10.1016/j.ygeno.2023.110638. https://pubmed.ncbi.nlm.nih.gov/37196931/

3. Jing, Nan, Du, Xinxing, Liang, Yu, Gao, Wei-Qiang, Fang, Yu-Xiang. 2024. PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility. In Journal of experimental & clinical cancer research : CR, 43, 144. doi:10.1186/s13046-024-03064-1. https://pubmed.ncbi.nlm.nih.gov/38745318/

4. Wu, Xuan, Chen, Chen, Han, Tiaotiao, Qiao, Longwei, Zheng, Qiping. 2023. Stat5a promotes Col10a1 gene expression during chondrocyte hypertrophic differentiation. In American journal of translational research, 15, 4006-4019. doi:. https://pubmed.ncbi.nlm.nih.gov/37434818/

5. Tian, Ye, Bi, Zhenhua, Ge, Shuaina, Ye, Bo, Han, Wenjie. 2022. STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy. In Clinical and experimental pharmacology & physiology, 49, 686-695. doi:10.1111/1440-1681.13644. https://pubmed.ncbi.nlm.nih.gov/35320597/

6. Nagenborg, Jan, Jin, Han, Ruder, Adele V, Donners, Marjo M P C, Biessen, Erik A L. 2023. GM-CSF-activated STAT5A regulates macrophage functions and inflammation in atherosclerosis. In Frontiers in immunology, 14, 1165306. doi:10.3389/fimmu.2023.1165306. https://pubmed.ncbi.nlm.nih.gov/37920458/

7. Li, Zhaoqing, Chen, Cong, Chen, Lini, Zhou, Jichun, Wang, Linbo. 2021. STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1. In Frontiers in oncology, 11, 697950. doi:10.3389/fonc.2021.697950. https://pubmed.ncbi.nlm.nih.gov/34336684/

8. Maninang, Christine, Li, Jinghong, Li, Willis X. . Expression and prognostic role of STAT5a across cancer types. In Bioscience reports, 43, . doi:10.1042/BSR20230612. https://pubmed.ncbi.nlm.nih.gov/37369132/