{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GAGE2A is a member of the cancer/testis antigen family that is normally restricted to germ cells but becomes aberrantly expressed in a variety of tumors. Accumulating evidence indicates that proteins in the GAGE family contribute to malignant progression by enhancing cell migration, invasion, and resistance to chemotherapy, as well as by participating in epigenetic and chromatin regulatory processes. For instance, loss‐of‐function studies using gene‐specific silencing in melanoma cells have demonstrated that reducing GAGE expression can markedly impede cell motility and invasive capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, biochemical analyses reveal that GAGE proteins interact with nuclear envelope regulatory factors and bind double‐stranded DNA in a sequence‐nonspecific manner; these findings suggest that GAGE proteins, including GAGE2A, may modulate chromatin organization and affect gene expression patterns in cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In hepatocellular carcinoma, GAGE2A has been identified within a multigene prognostic signature, implicating its increased expression in the aggressive behavior and poor outcome of tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, other studies have linked the upregulation of neighboring GAGE family members with the acquisition of resistance to chemotherapeutic agents, supporting a role for GAGE2A in facilitating tumor survival under pharmacologic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, the immunogenic properties of GAGE antigens have been well documented; due to their restricted expression in normal tissues outside the testis and robust recognition by cytotoxic T cells, GAGE2A and related proteins represent promising targets for immunotherapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Otavia L Caballero, Tzeela Cohen, Sita Gurung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of CT-Xp gene knock down in melanoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.921"}], "href": "https://doi.org/10.18632/oncotarget.921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23625514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23625514"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Morten F Gjerstorff, Heike I Rösner, Christina B Pedersen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)."}]}, {"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.0045819"}], "href": "https://doi.org/10.1371/journal.pone.0045819"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23029259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23029259"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laner Shi, Xin Shang, Kechao Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of potential crucial genes associated with the pathogenesis and prognosis of liver hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Pathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jclinpath-2020-206979"}], "href": "https://doi.org/10.1136/jclinpath-2020-206979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33004423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33004423"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhenfeng Duan, Yifei Duan, Diana E Lamendola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12855658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12855658"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "B Van den Eynde, O Peeters, O De Backer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (1995)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.182.3.689"}], "href": "https://doi.org/10.1084/jem.182.3.689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7544395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7544395"}]}]}]}