Sulf1, also known as Sulfatase 1, is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans. It plays a critical role in biological regulation by modulating the bio-availability of various signaling molecules. Sulf1 is involved in multiple pathways such as TGF-β1/SMAD, FAK/PI3K/AKT/mTOR, and Wnt signaling, influencing important biological processes like cell proliferation, migration, and fibrosis [1,2,3,4]. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying Sulf1's function.

In idiopathic pulmonary fibrosis, Sulf1 is upregulated in lung tissues of patients. Knockdown of Sulf1 in HFL1 cells using lentiviral-delivered shRNA suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-β1-driven and non-TGF-β1-driven conditions, indicating that Sulf1 promotes fibrosis through the TGF-β1/SMAD pathway [1]. In colorectal cancer, knockdown of Sulf1 inhibited cell proliferation, invasion, and migration, and increased apoptosis, suggesting that Sulf1 promotes CRC progression via the FAK/PI3K/AKT/mTOR signaling pathway [2]. In bone metastatic prostate cancer, SULF1 knockout fibroblastic cells in a 3D model showed increased Wnt3A-driven growth of PCa cells, indicating that SULF1 can suppress Wnt3A-driven growth signals in the desmoplastic stroma of PCa bone metastases [3].

In conclusion, Sulf1 has diverse functions in different biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in fibrosis, cancer progression, and metastasis. Understanding Sulf1's function provides potential therapeutic targets for diseases like idiopathic pulmonary fibrosis, colorectal cancer, and bone metastatic prostate cancer.

References:

1. Tu, Meng, Lu, Chunya, Jia, Hongxia, Yang, Ming, Zhang, Guojun. 2024. SULF1 expression is increased and promotes fibrosis through the TGF-β1/SMAD pathway in idiopathic pulmonary fibrosis. In Journal of translational medicine, 22, 885. doi:10.1186/s12967-024-05698-3. https://pubmed.ncbi.nlm.nih.gov/39354547/

2. Zhu, Wenjie, Wu, Changlei, Liu, Zitao, Cheng, Xiufeng, Huang, Jun. 2024. SULF1 regulates malignant progression of colorectal cancer by modulating ARSH via FAK/PI3K/AKT/mTOR signaling. In Cancer cell international, 24, 201. doi:10.1186/s12935-024-03383-5. https://pubmed.ncbi.nlm.nih.gov/38844922/

3. Brasil da Costa, Fabio Henrique, Lewis, Michael S, Truong, Anna, Carson, Daniel D, Farach-Carson, Mary C. 2020. SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models. In PloS one, 15, e0230354. doi:10.1371/journal.pone.0230354. https://pubmed.ncbi.nlm.nih.gov/32413029/

4. Fellgett, Simon W, Maguire, Richard J, Pownall, Mary Elizabeth. 2015. Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling. In Journal of cell science, 128, 1408-21. doi:10.1242/jcs.164467. https://pubmed.ncbi.nlm.nih.gov/25681501/