{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM45A is a transmembrane protein that has emerged as an important mediator in tumor cell survival under stress conditions. In breast cancer, for example, hypoxia—commonly found in solid tumors—induces mechanisms that promote therapeutic resistance, with TMEM45A being implicated in these adaptive responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several cancers, TMEM45A behaves as an oncogene. In ovarian cancer, its overexpression is associated with increased cell proliferation, G1 cell cycle progression, enhanced adhesion, and invasion, along with the upregulation of key mediators of the TGF‑β pathway and RhoA/ROCK2 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In gliomas, high TMEM45A levels correlate with advanced tumor grades, poor patient survival, and augmented migratory and invasive capabilities through regulation of cell cycle proteins such as Cyclin D1, CDK4, and PCNA."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Studies in colorectal cancer have demonstrated that TMEM45A overexpression contributes to chemoresistance by promoting epithelial–mesenchymal transition (EMT) and activating TGF‑β signaling, whereas its silencing enhances drug sensitivity, increases intracellular drug accumulation, and downregulates MDR1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, in head and neck squamous cell carcinoma (and renal cell carcinoma), modulation of TMEM45A has been linked to altered cisplatin sensitivity, underscoring its context‐dependent roles in apoptosis regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Additional work in glioma models further confirms that TMEM45A promotes proliferation, migration, and invasion via the NF‑κB pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and in cervical cancer, its silencing reverses cisplatin resistance while inducing cell cycle arrest and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In gastric cancer, TMEM45A overexpression is not only a marker of poor prognosis but is also associated with increased immune cell infiltration, making it a potentially reliable prognostic indicator."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in oncogenesis, TMEM45A is also involved in normal cellular differentiation. In the epidermis, its expression is upregulated during keratinocyte differentiation, with localization in the trans‐Golgi network of the granular layer, thereby linking TMEM45A to the process of keratinization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lionel Flamant, Edith Roegiers, Michael Pierre, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of TMEM45A inhibits the proliferation, migration and invasion of glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26722455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26722455"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mo Zhu, Baofei Jiang, Dongsheng Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of TMEM45A overcomes multidrug resistance and epithelial-mesenchymal transition in human colorectal cancer cells through inhibition of TGF-β signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Pharmacol Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1440-1681.13220"}], "href": "https://doi.org/10.1111/1440-1681.13220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31788833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31788833"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kathleen Schmit, Jia-Wei Chen, Sophie Ayama-Canden, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pan-cancer analysis of TMEM45A and exploration of its prognostic value and mechanism in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol (Noisy-le-grand) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14715/cmb/2024.70.7.32"}], "href": "https://doi.org/10.14715/cmb/2024.70.7.32"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39097870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39097870"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aurélie Hayez, Jérémy Malaisse, Edith Roegiers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High TMEM45A expression is correlated to epidermal keratinization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.12403"}], "href": "https://doi.org/10.1111/exd.12403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24689342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24689342"}]}]}]}