{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Frizzled‐1 (FZD1) is emerging as a pivotal receptor mediating canonical Wnt/β‐catenin signaling in a context‐dependent manner. For instance, in bone tissue, continuous parathyroid hormone stimulation upregulates FZD1 expression, thereby enhancing β‐catenin accumulation and promoting osteogenic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In lung development, FZD1, in concert with FZD10, serves as a key receptor for Wnt7b that drives canonical signaling required for proper airway and vascular formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, aberrant FZD1 expression has been linked to cancer biology: in neuroblastoma cells, overexpression of FZD1 sustains Wnt/β‐catenin activity, transactivating targets such as MDR1 and thereby contributing to chemoresistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while in multidrug‐resistant breast cancer cells, elevated FZD1 levels similarly promote resistance to chemotherapy through this pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n FZD1 also plays a role in modulating proliferative responses; for example, in vascular smooth muscle cells, Wnt4 engages FZD1 to stimulate proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the context of embryonic development, FZD1 is a direct transcriptional target of p53 family proteins, and its induction is critical for proper mesendoderm differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, innate immune activation (via TLR/NF-κB signaling) upregulates FZD1 in macrophages, suggesting its participation in balancing inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, studies using the human Frizzled 1 (HFz1) receptor confirm its capacity to transmit canonical Wnt-3a signals"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "; however, FZD1-dependent signaling can be repressed when LRP1 sequesters HFz1 and prevents productive receptor–coreceptor complex formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Together, these findings underscore FZD1 as a versatile mediator of canonical Wnt signaling whose regulation is integral to diverse physiological processes—including development, cell proliferation, and drug resistance—and whose dysregulation may contribute to disease states.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1, 2, 3, 4, 5, 6, 7, 8, 9)\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N H Kulkarni, D L Halladay, R R Miles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of parathyroid hormone on Wnt signaling pathway in bone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.20506"}], "href": "https://doi.org/10.1002/jcb.20506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15962290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15962290"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhishan Wang, Weiguo Shu, Min Min Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.12.5022-5030.2005"}], "href": "https://doi.org/10.1128/MCB.25.12.5022-5030.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15923619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15923619"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M Flahaut, R Meier, A Coulon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/beta-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.80"}], "href": "https://doi.org/10.1038/onc.2009.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19421142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19421142"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hui Zhang, Xiaofang Zhang, Xiaojuan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interference of Frizzled 1 (FZD1) reverses multidrug resistance in breast cancer cells through the Wnt/β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2012.03.039"}], "href": "https://doi.org/10.1016/j.canlet.2012.03.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22484497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22484497"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aikaterini Tsaousi, Helen Williams, Cressida A Lyon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt4/β-catenin signaling induces VSMC proliferation and is associated with intimal thickening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.110.233999"}], "href": "https://doi.org/10.1161/CIRCRESAHA.110.233999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21193738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21193738"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qiong Wang, Yilong Zou, Sonja Nowotschin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The p53 Family Coordinates Wnt and Nodal Inputs in Mesendodermal Differentiation of Embryonic Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2016.10.002"}], "href": "https://doi.org/10.1016/j.stem.2016.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27889317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27889317"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jan Neumann, Kolja Schaale, Katja Farhat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frizzled1 is a marker of inflammatory macrophages, and its ligand Wnt3a is involved in reprogramming Mycobacterium tuberculosis-infected macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.10-160994"}], "href": "https://doi.org/10.1096/fj.10-160994"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20667980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20667980"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tamar Golan, Abraham Yaniv, Anna Bafico, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human Frizzled 6 (HFz6) acts as a negative regulator of the canonical Wnt. beta-catenin signaling cascade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M306421200"}], "href": "https://doi.org/10.1074/jbc.M306421200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14747478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14747478"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alona Zilberberg, Abraham Yaniv, Arnona Gazit "}, {"type": "b", "children": [{"type": "t", "text": "The low density lipoprotein receptor-1, LRP1, interacts with the human frizzled-1 (HFz1) and down-regulates the canonical Wnt signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M311292200"}], "href": "https://doi.org/10.1074/jbc.M311292200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14739301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14739301"}]}]}]}