Ltf, which encodes lactotransferrin, is an iron-binding transport protein. It is involved in multiple biological processes, such as iron metabolism, immune response, and inflammation regulation [1,2,3,5,6]. It is associated with pathways like the JAK/STAT3, NF-κB, and ubiquitin-proteasome systems, and has significance in various diseases including cancer, neurodegenerative conditions, and degenerative disorders [1,2,3,5,6,7,8,9]. Genetic models, especially knockout (KO) mouse models, can be valuable in studying its function.

In hepatocellular carcinoma (HCC), METTL16-SENP3 axis promotes LTF expression. Elevated LTF chelates free iron, reducing liable iron pool level and conferring ferroptosis resistance and tumorigenesis [1]. In hyperglycemic mice with intracerebral hemorrhagic stroke, lack of neutrophilic Ltf transcription and secretion exacerbates neuronal ferroptosis, while recombinant Ltf administration protects against it [3]. In osteosarcoma, overexpression of LTF promotes cell proliferation, migration, and invasion, suggesting it may serve as a prognostic biomarker [4].

In summary, Ltf is crucial in iron-related processes and immune-related responses. Studies using KO mouse models, like those in HCC and stroke, have revealed its role in ferroptosis-related disease conditions, providing insights into potential therapeutic strategies for treating related diseases.

References:

1. Wang, Jialin, Xiu, Mengxi, Wang, Jin, Gao, Yong, Li, Yandong. 2024. METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma. In Journal of hematology & oncology, 17, 78. doi:10.1186/s13045-024-01599-6. https://pubmed.ncbi.nlm.nih.gov/39218945/

2. Qiu, Kai, Ding, Daling, Zhang, Fengjiang, Yang, Bo. 2024. LTF as a Potential Prognostic and Immunological Biomarker in Glioblastoma. In Biochemical genetics, , . doi:10.1007/s10528-024-10716-6. https://pubmed.ncbi.nlm.nih.gov/38763993/

3. Xiao, Zhongnan, Shen, Danmin, Lan, Ting, Yang, Fei, Li, Qian. 2022. Reduction of lactoferrin aggravates neuronal ferroptosis after intracerebral hemorrhagic stroke in hyperglycemic mice. In Redox biology, 50, 102256. doi:10.1016/j.redox.2022.102256. https://pubmed.ncbi.nlm.nih.gov/35131600/

4. Liu, Xiaoqi, Wang, Zengqiang, Liu, Meijiao, Liu, Bing, Jiang, Yanan. 2022. Identification of LTF as a Prognostic Biomarker for Osteosarcoma. In Journal of oncology, 2022, 4656661. doi:10.1155/2022/4656661. https://pubmed.ncbi.nlm.nih.gov/35096061/

5. Wang, Yuan, Liu, Yang, Liu, Jiao, Kang, Rui, Tang, Daolin. 2020. NEDD4L-mediated LTF protein degradation limits ferroptosis. In Biochemical and biophysical research communications, 531, 581-587. doi:10.1016/j.bbrc.2020.07.032. https://pubmed.ncbi.nlm.nih.gov/32811647/

6. Li, Tao, Liu, Yuchi, Cao, Jian, Jia, Jingyu, Cheng, Xigao. . LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway. In Journal of cellular and molecular medicine, 28, e18267. doi:10.1111/jcmm.18267. https://pubmed.ncbi.nlm.nih.gov/39392081/

7. Wen, Junmiao, Zheng, Wang, Zeng, Liang, Chen, Jiayan, Fan, Min. 2023. LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma. In International journal of biological sciences, 19, 1509-1527. doi:10.7150/ijbs.78669. https://pubmed.ncbi.nlm.nih.gov/37056929/

8. Zhao, Qi, Cheng, Yingying, Xiong, Ying. 2021. LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway. In Frontiers in oncology, 11, 692117. doi:10.3389/fonc.2021.692117. https://pubmed.ncbi.nlm.nih.gov/34868909/

9. Zhang, Jun, Zhu, Jiayong, Zhao, Boming, Li, Bin, Chen, Biao. 2023. LTF induces senescence and degeneration in the meniscus via the NF-κB signaling pathway: A study based on integrated bioinformatics analysis and experimental validation. In Frontiers in molecular biosciences, 10, 1134253. doi:10.3389/fmolb.2023.1134253. https://pubmed.ncbi.nlm.nih.gov/37168259/