{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies aimed at identifying candidate tumor‐suppressor genes in breast and prostate carcinogenesis have revealed that epigenetic silencing via promoter hypermethylation may underlie the downregulation of genes normally expressed in epithelial cells. Among these candidates, TSHZ2 has emerged as a gene whose expression is notably reduced in cancer cell lines, suggesting that its loss could contribute to neoplastic transformation and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses in breast-derived cells further demonstrated that TSHZ2 encodes a nuclear zinc‐finger homeobox protein with a bipartite nuclear localization signal and acts as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. By nucleating a complex with factors such as CtBP2 and by suppressing the transcriptional activity of GLI1—a key effector of Hedgehog signaling—TSHZ2 regulates the expression of genes like AEBP1 and CXCR4 that are involved in cell migration and tumor progression. These findings support a role for TSHZ2 as an important negative regulator of oncogenic pathways in mammary tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its function in transcriptional repression, TSHZ2 has been implicated in cell cycle control and tumor suppression. Prolonged epidermal growth factor stimulation uncovers a delayed down-regulated expression of TSHZ2, and overexpression experiments in mammary cells have demonstrated that TSHZ2 can inhibit tumor growth and metastasis by orchestrating a multiprotein complex that includes key mitotic regulators such as PRC1 and cyclin B1. Moreover, studies in lung adenocarcinoma have found that higher levels of TSHZ2 correlate with reduced cell proliferation, diminished migratory capacity, and improved patient prognosis, underscoring its potential as a therapeutic target. Although other members of the teashirt family—such as TSHZ3, which when lost leads to congenital urinary tract malformations—highlight the importance of this family in developmental processes, the specific tumor suppressive activities of TSHZ2 in adult tissues appear to be mediated through tight control of transcription and the cell cycle."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Miyako Yamamoto, Emili Cid, Samuel Bru, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare and frequent promoter methylation, respectively, of TSHZ2 and 3 genes that are both downregulated in expression in breast and prostate cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0017149"}], "href": "https://doi.org/10.1371/journal.pone.0017149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21423795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21423795"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miho Riku, Shingo Inaguma, Hideaki Ito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6788"}], "href": "https://doi.org/10.18632/oncotarget.6788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26744317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26744317"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mary L Uribe, Maik Dahlhoff, Rajbir N Batra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TSHZ2 is an EGF-regulated tumor suppressor that binds to the cytokinesis regulator PRC1 and inhibits metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.abe6156"}], "href": "https://doi.org/10.1126/scisignal.abe6156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34158398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34158398"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shilei Zhao, Xin Guo, Ken-Ichi Mizutani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Teashirt Homolog 2 suppresses cell proliferation and predicts the favorable survival of Lung Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.52109"}], "href": "https://doi.org/10.7150/ijms.52109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33850468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33850468"}]}]}]}