{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in breast and other epithelial cancers have identified a transmembrane phosphatidate phosphatase—referred to in these reports as PPAPDC1B—that is frequently overexpressed as a result of amplification of the chromosomal 8p11–12 region. Functional analyses following RNA interference indicate that this enzyme promotes cell survival and malignant transformation, as evidenced by its ability to confer anchorage‐independent growth and to activate multiple signaling cascades, including the Janus-activated kinase–signal transducer and activator of transcription (JAK–STAT), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC) pathways. Moreover, its inhibition has been shown to dramatically reduce xenograft tumor growth, positioning it as a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, another phosphatidic acid phosphatase gene from the same chromosomal region—HTPAP—has been characterized as a metastasis suppressor in hepatocellular carcinoma. A series of investigations demonstrate that reduced expression of HTPAP, whether due to chromosomal deletion, unfavorable promoter polymorphisms, or differential transcript expression (with one variant, HTPAP-1, being particularly significant), correlates with enhanced invasive behavior, increased metastasis, and poorer clinical outcomes. These findings delineate a critical, context-dependent role for phosphatase activity in tumor progression, where HTPAP functions to restrain metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA related body of work has identified additional members of the mammalian phosphatidate phosphatase family—DPPL1 and DPPL2—that, while sharing a broader substrate specificity (with a preference for diacylglycerol pyrophosphate), further underline the diverse roles of lipid phosphatases in cellular physiology. These enzymes, exhibiting distinct cofactor requirements and sensitivity to N-ethylmaleimide, are expressed in a tissue-specific manner and highlight the complexity of lipid signaling regulation in both normal and pathologic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabelle Bernard-Pierrot, Nadège Gruel, Nicolas Stransky, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PPAPDC1B and WHSC1L1 are common drivers of the 8p11-12 amplicon, not only in breast tumors but also in pancreatic adenocarcinomas and lung tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.07.028"}], "href": "https://doi.org/10.1016/j.ajpath.2013.07.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24051013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24051013"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "X Wu, H-L Jia, Y-F Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209191"}], "href": "https://doi.org/10.1038/sj.onc.1209191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16261160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16261160"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chun Dai, Qiong-Zhu Dong, Ning Ren, et al. 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