{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Family with sequence similarity 135 member B (FAM135B) appears to have context‐dependent roles in human disease. In esophageal squamous cell carcinoma (ESCC), FAM135B is frequently overexpressed relative to normal mucosa and its high expression correlates with advanced clinical stage, lymph node metastasis, and radio‐resistance. Functional studies in ESCC cell models indicate that FAM135B promotes colony formation and cell cycle progression—likely through regulation of the PI3K/Akt/mTOR signaling pathway—thereby contributing to tumor progression and reduced sensitivity to irradiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, studies in a neurodegenerative context have revealed that FAM135B supports neuronal health; markedly decreased expression of FAM135B in spinal and bulbar muscular atrophy (SBMA) motor neurons was associated with neurite defects and diminished cell survival, and experimental knockdown of FAM135B in wild‐type motor neurons recapitulated these degenerative phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, genetic association studies have implicated FAM135B in modulating cell signaling activities linked to immune function; a specific single nucleotide variant in FAM135B was found to be more prevalent in individuals with extrapulmonary tuberculosis compared to those with pulmonary tuberculosis, suggesting that FAM135B may also influence susceptibility to infectious disease through effects on cell signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that FAM135B functions as a context‐dependent modulator: acting as an oncogenic driver in ESCC by enhancing tumor cell proliferation, survival, and radioresistance, while also serving a neuroprotective role in motor neurons. Further investigation into its molecular mechanisms may provide novel diagnostic and therapeutic opportunities.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Liangwen Bi, Haijing Wang, Ye Tian "}, {"type": "b", "children": [{"type": "t", "text": "Silencing FAM135B enhances radiosensitivity of esophageal carcinoma cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2020.145358"}], "href": "https://doi.org/10.1016/j.gene.2020.145358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33340561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33340561"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tingting Wang, Xiaoyan Lv, Shen Jiang, et al. 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