Postn-KO Mouse

Postn, also known as periostin, is an extracellular matrix protein. It is involved in multiple biological processes such as extracellular matrix remodeling, cell adhesion, and migration. It is associated with pathways like the Wnt/β-catenin, IL-6/STAT3, and NF-κB signaling pathways, which are crucial for normal tissue development and in disease-related processes [3,5]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable in studying its function.

In cancer, POSTN+ cancer-associated fibroblasts (CAFs) are significant. In hepatocellular carcinoma, they act as immune response barriers, hindering T-cell infiltration and reducing immunotherapy efficacy. They also interact with SPP1+ macrophages via the IL-6/STAT3 pathway, creating an immunosuppressive microenvironment [1]. In non-small cell lung cancer, POSTN+ CAFs are enriched in advanced tumors, related to extracellular matrix remodeling, tumor invasion, and immune suppression. They localize closely with SPP1+ macrophages, associated with T-cell exhaustion and poor prognosis [2]. In gastric cancer, POSTN secreted by extracellular matrix CAFs enhances macrophage chemotaxis through the Akt signaling pathway, leading to immune checkpoint blockade resistance [6]. In neuroblastoma, ALK drives tumorigenesis in part through a feedforward loop between POSTN and WNT signaling [4].

In summary, Postn is essential for extracellular matrix-related functions and is involved in multiple disease-associated signaling pathways. Studies using KO/CKO mouse models (although not explicitly detailed in the provided references) would likely further clarify its role in diseases like cancer, where it contributes to tumor progression, immune evasion, and treatment resistance. Understanding Postn's function can potentially offer new therapeutic strategies for these diseases.

References:

1. Wang, Hao, Liang, Yuan, Liu, Zheng, Zhao, Haitao, Lu, Ling. 2024. POSTN+ cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2023-008721. https://pubmed.ncbi.nlm.nih.gov/39067872/

2. Chen, Chao, Guo, Qiang, Liu, Yang, Liu, Jixian, Xu, Qumiao. . Single-cell and spatial transcriptomics reveal POSTN+ cancer-associated fibroblasts correlated with immune suppression and tumour progression in non-small cell lung cancer. In Clinical and translational medicine, 13, e1515. doi:10.1002/ctm2.1515. https://pubmed.ncbi.nlm.nih.gov/38115703/

3. Yu, Yue, Tan, Chang-Ming, Jia, Yuan-Yuan. 2021. Research status and the prospect of POSTN in various tumors. In Neoplasma, 68, 673-682. doi:10.4149/neo_2021_210223N239. https://pubmed.ncbi.nlm.nih.gov/34348466/

4. Huang, Miller, Fang, Wanqi, Farrel, Alvin, Maris, John M, Weiss, William A. 2024. ALK upregulates POSTN and WNT signaling to drive neuroblastoma. In Cell reports, 43, 113927. doi:10.1016/j.celrep.2024.113927. https://pubmed.ncbi.nlm.nih.gov/38451815/

5. Zhu, Daxue, Chen, Shijie, Sheng, Pan, Li, Yanhu, Kang, Xuewen. 2024. POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/β-catenin and NF-κB signal pathway in intervertebral disc degeneration. In Cellular signalling, 121, 111277. doi:10.1016/j.cellsig.2024.111277. https://pubmed.ncbi.nlm.nih.gov/38944256/

6. You, Tingting, Tang, Hui, Wu, Wenjing, Sun, Zhao, Zhao, Robert Chunhua. 2023. POSTN Secretion by Extracellular Matrix Cancer-Associated Fibroblasts (eCAFs) Correlates with Poor ICB Response via Macrophage Chemotaxis Activation of Akt Signaling Pathway in Gastric Cancer. In Aging and disease, 14, 2177-2192. doi:10.14336/AD.2023.0503. https://pubmed.ncbi.nlm.nih.gov/37199594/