{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLPP2, a member of the phospholipid phosphatase family, catalyzes the dephosphorylation of lipid substrates, such as phosphatidic acid, and is implicated in both lipid biosynthesis and cellular signal transduction. Initial studies in mice revealed that although its ortholog (Ppap2c) performs these key biochemical reactions, its deletion does not appear to disrupt embryonic development or fertility, suggesting potential compensatory mechanisms or context‐dependent functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cultured cells, modulation of PLPP2 levels has pronounced effects on cell cycle progression and proliferation. Specifically, knock-down of PLPP2 delays cyclin A accumulation and S-phase entry, while its overexpression accelerates these events, indicating that PLPP2 plays a regulatory role in G1/S transition. Additionally, studies have demonstrated that lipid phosphate phosphatases, including PLPP2, can form functional homo- and hetero-oligomers, potentially conferring spatial regulation of phosphatidic acid and sphingosine 1-phosphate signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer biology, PLPP2 has emerged as a pro-tumorigenic factor. Elevated PLPP2 expression is associated with increased cell proliferation and tumor growth in breast cancer, where it appears to influence the expression of key regulators such as cyclins, cell cycle inhibitors, and even c-Myc. Knockout studies in breast cancer cell lines have shown that loss of PLPP2 compromises G1/S progression and tumor formation, while overexpression correlates with poorer patient outcomes, particularly in estrogen receptor-positive breast cancers. These findings highlight PLPP2 as a potential therapeutic target in malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWhile efforts in other fields, such as the enhanced detection of early-stage lung adenocarcinoma via image-based screening, underline the broader challenge of accurately defining tumor markers and reducing over-treatment, these advances also accentuate the importance of identifying precise molecular determinants. Although this study did not directly address PLPP2, the development of such diagnostic tools reinforces the need for further investigation into molecules like PLPP2 that are pivotal in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N Zhang, J P Sundberg, T Gridley "}, {"type": "b", "children": [{"type": "t", "text": "Mice mutant for Ppap2c, a homolog of the germ cell migration regulator wunen, are viable and fertile."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genesis (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1526-968x(200008)27:4"}, {"type": "a", "children": [{"type": "t", "text": "137::aid-gene10"}], "href": "137::aid-gene10"}, {"type": "t", "text": "3.0.co;2-4"}], "href": "https://doi.org/10.1002/1526-968x(200008"}, {"type": "t", "text": "27:4"}, {"type": "a", "children": [{"type": "t", "text": "137::aid-gene10"}], "href": "137::aid-gene10"}, {"type": "t", "text": "3.0.co;2-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10992322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10992322"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katherine E Morris, Luis M Schang, David N Brindley "}, {"type": "b", "children": [{"type": "t", "text": "Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511710200"}], "href": "https://doi.org/10.1074/jbc.M511710200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16467304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16467304"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jaclyn S Long, Nigel J Pyne, Susan Pyne "}, {"type": "b", "children": [{"type": "t", "text": "Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic competency, subcellular distribution and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20071607"}], "href": "https://doi.org/10.1042/BJ20071607"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18215144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18215144"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoyun Tang, Christopher R Cromwell, Rongzong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipid phosphate phosphatase-2 promotes tumor growth through increased c-Myc expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.66230"}], "href": "https://doi.org/10.7150/thno.66230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35966578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35966578"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhenming Wang, Huimin Qi, Yuping Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLPP2: Potential therapeutic target of breast cancer in PLPP family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunobiology (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.imbio.2022.152298"}], "href": "https://doi.org/10.1016/j.imbio.2022.152298"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36332491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36332491"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yibei Wang, Ziwei Miao, Xiaoxue Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-023-02877-w"}], "href": "https://doi.org/10.1186/s13046-023-02877-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37996944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37996944"}]}]}]}