{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts mention PLPPR3 directly, they consistently describe the functions of a related protein commonly known as DLC2 (also referred to as STARD13 or START‐GAP2). In the context of cancer, studies show that DLC2 acts as a metastasis suppressor. For instance, one study demonstrated that miR‐125b promotes metastasis in breast cancer cells by targeting STARD13, leading to enhanced migratory potential, while another study using a Neu oncogene‐induced mammary tumor model revealed that loss of Stard13 increased lung metastases without affecting primary tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther investigations focused on the cellular mechanisms of DLC2 highlight its role as a RhoGAP that negatively regulates RhoA (and, to a lesser extent, Cdc42) activity, thereby modulating the actin cytoskeleton. Studies in fibroblasts and pancreatic β‐cells have shown that expression of DLC2 isoforms induces dramatic changes in cell morphology and suppresses stress fiber formation, effects that are attributed to decreased RhoA activity. These findings underscore the importance of DLC2 in cytoskeletal reorganization and cellular function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, DLC2 has been implicated in the modulation of pain signalling. Studies using DLC2‐deficient mice have revealed that the loss of DLC2 leads to enhanced inflammatory pain responses, a consequence of increased RhoA activity and downstream ROCK/p38 MAPK activation. These changes result in elevated expression of pro‐inflammatory mediators and enhanced microglial activation in the spinal dorsal horn, indicating that DLC2’s inhibitory effect on RhoA is central to controlling inflammation-induced hyperalgesia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Feng Tang, Rui Zhang, Yunmian He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-125b induces metastasis by targeting STARD13 in MCF-7 and MDA-MB-231 breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0035435"}], "href": "https://doi.org/10.1371/journal.pone.0035435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22693547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22693547"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pratima Basak, Heather Leslie, Rachelle L Dillon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in ErbB2 (Neu) oncogene induced mouse mammary tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.22519"}], "href": "https://doi.org/10.1002/gcc.22519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29218825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29218825"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Thomas Ho-Yin Leung, Yick-Pang Ching, Judy Wai Ping Yam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0504501102"}], "href": "https://doi.org/10.1073/pnas.0504501102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16217026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16217026"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Katsuhisa Kawai, Jun-ichi Seike, Takuya Iino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "START-GAP2/DLC2 is localized in focal adhesions via its N-terminal region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.01.095"}], "href": "https://doi.org/10.1016/j.bbrc.2009.01.095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19250640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19250640"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heike Naumann, Thomas Rathjen, Matthew N Poy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RhoGAP Stard13 controls insulin secretion through F-actin remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Metab (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmet.2017.12.013"}], "href": "https://doi.org/10.1016/j.molmet.2017.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29310936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29310936"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fred K C Chan, Stephen S M Chung, Irene O Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RhoA GTPase-activating protein DLC2 modulates RhoA activity and hyperalgesia to noxious thermal and inflammatory stimuli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosignals (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000331240"}], "href": "https://doi.org/10.1159/000331240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22204965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22204965"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Stanley Sau Ching Wong, Un Man Lee, Xiao-Min Wang, et al. 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