Pear1, also known as platelet endothelial aggregation receptor 1, is a key receptor that plays vital roles in hemostasis by causing platelet adhesion and initiating platelet aggregation [2]. It is involved in multiple signaling pathways, such as associating with Protein Phosphatase 1 to suppress fibrotic factors-induced intracellular signaling [1]. Its functions are crucial in various biological processes and diseases.

In aged mice, Pear1 deficiency spontaneously leads to alveolar collagens accumulation, and mesenchyme-specific Pear1 deficiency aggravates bleomycin-induced pulmonary fibrosis, indicating its role in modulating pulmonary fibrosis progression through regulating mesenchymal cell function [1]. In triple-negative breast cancer (TNBC), levels of PEAR1 protein and PEAR1 phosphorylation at Ser891 are increased, and are negatively correlated with overall survival, suggesting its role in TNBC metastasis [3]. In acute myeloid leukemia (AML), PEAR1 is among the strongest predictors of patient survival, especially for young patients [4].

In conclusion, Pear1 is essential for hemostasis and has significant implications in diseases like pulmonary fibrosis, TNBC, and AML. Gene knockout (KO) or conditional knockout (CKO) mouse models have been valuable in revealing its role in these disease conditions, enhancing our understanding of the underlying molecular mechanisms and potentially guiding future therapeutic strategies.

References:

1. Geng, Yan, Li, Lin, Yan, Jie, Liu, Junling, Fan, Xuemei. 2022. PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis. In Nature communications, 13, 7114. doi:10.1038/s41467-022-34870-w. https://pubmed.ncbi.nlm.nih.gov/36402779/

2. Ansari, Narges, Najafi, Sahar, Shahrabi, Saied, Saki, Najmaldin. . PEAR1 polymorphisms as a prognostic factor in hemostasis and cardiovascular diseases. In Journal of thrombosis and thrombolysis, 51, 89-95. doi:10.1007/s11239-020-02149-w. https://pubmed.ncbi.nlm.nih.gov/32445063/

3. Shen, Yingzhi, Yan, Jie, Li, Lin, Liu, Junling, Fan, Xuemei. 2024. LOXL2-induced PEAR1 Ser891 phosphorylation suppresses CD44 degradation and promotes triple-negative breast cancer metastasis. In The Journal of clinical investigation, 134, . doi:10.1172/JCI177357. https://pubmed.ncbi.nlm.nih.gov/39145451/

4. Bottomly, Daniel, Long, Nicola, Schultz, Anna Reister, McWeeney, Shannon K, Tyner, Jeffrey W. 2022. Integrative analysis of drug response and clinical outcome in acute myeloid leukemia. In Cancer cell, 40, 850-864.e9. doi:10.1016/j.ccell.2022.07.002. https://pubmed.ncbi.nlm.nih.gov/35868306/