{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HTATIP2 (also known as TIP30 or CC3) is a multifunctional tumor‐suppressor protein that plays a critical role in modulating oncogenic transcription, apoptosis, metastasis, and cellular metabolic responses. HTATIP2 can repress oncogenic transcription—for example, by inhibiting estrogen receptor–mediated activation of the proto‐oncogene c‑myc—and its loss or downregulation potentiates aberrant growth signaling and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In several tumor types, including hepatocellular and gastric carcinomas, epigenetic silencing of the HTATIP2 gene—often through promoter hypermethylation—correlates with enhanced invasion, metastasis, and poor clinical outcome; this is associated with the upregulation of pro‐invasive factors such as osteopontin and matrix metalloproteinases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition, HTATIP2 influences critical nuclear transport processes; for instance, its inhibitory action on Importin‐mediated nuclear entry can restrict the nuclear localization of proteins required for differentiation and proapoptotic signaling, thereby impacting epithelial–mesenchymal transition and cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In lung adenocarcinoma models, HTATIP2 deficiency delays degradation of activated epidermal growth factor receptor (EGFR), prolonging downstream signaling and facilitating tumor initiation and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, loss of HTATIP2 contributes to metabolic adaptation under nutrient stress, thereby endowing tumor cells with enhanced survival and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, studies in mammary epithelial cells indicate that reduced HTATIP2 expression favors hyperproliferation, suggesting that its intact function is essential to restrain neoplastic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the importance of HTATIP2 as a central regulator of key cellular processes that restrain tumor progression and metastasis. Restoration or maintenance of HTATIP2 function may therefore represent a promising therapeutic strategy to improve treatment responses and patient outcomes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chao Jiang, Mitsuhiro Ito, Valerie Piening, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M401809200"}], "href": "https://doi.org/10.1074/jbc.M401809200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15073177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15073177"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xin Tong, Kai Li, Zhigang Luo, et al. 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