{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch using murine models demonstrates that Testin (TES) acts as a potent tumor suppressor. In these studies, loss of TES function was associated with dramatically increased susceptibility to carcinogen‐induced lesions including papillomas and carcinomas, indicating that TES normally limits abnormal cell proliferation and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have revealed that TES shares homologous domains with known planar cell polarity regulators—most notably, Prickle (Pk)—thereby suggesting a potential role in establishing and maintaining coordinated cellular orientation across tissues, although its precise function in this context remains to be fully elucidated in mammals."}, {"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 cardiovascular system, TES appears crucial in modulating pathological cardiac remodeling. Experimental overexpression of TES in murine hearts mitigated hypertrophy, ventricular dilation, dysfunction, and fibrosis by directly interacting with calcineurin and inhibiting its downstream hypertrophic signaling, highlighting a protective role in cardiac stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, TES has been implicated in the regulation of focal adhesion dynamics. Through its interaction with the LIM domain protein zyxin, TES is recruited to focal adhesions where it assists in the modulation of the actin cytoskeleton and influences cell spreading. Disruption of the zyxin-TES interaction alters adhesion turnover, underscoring TES’s multifaceted contribution to cell motility and structural organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alessandra Drusco, Nicola Zanesi, Claudia Roldo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockout mice reveal a tumor suppressor function for Testin."}]}, {"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.0504934102"}], "href": "https://doi.org/10.1073/pnas.0504934102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16033868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16033868"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dong-Dong Ren, Michael Kelly, Sun Myoung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testin interacts with vangl2 genetically to regulate inner ear sensory cell orientation and the normal development of the female reproductive tract in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.24042"}], "href": "https://doi.org/10.1002/dvdy.24042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23996638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23996638"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lu Gao, Yuan Liu, Sen Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testin protects against cardiac hypertrophy by targeting a calcineurin-dependent signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13934"}], "href": "https://doi.org/10.1111/jcmm.13934"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30467953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30467953"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ermin Hadzic, Marie Catillon, Aliaksandr Halavatyi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0140511"}], "href": "https://doi.org/10.1371/journal.pone.0140511"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26509500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26509500"}]}]}]}