{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LEM domain‐containing 1 (LEMD1) is emerging as an oncogenic cancer–testis antigen that is normally restricted to germ cells but is aberrantly re‐expressed in a variety of human tumors. Its transcriptional activation has been observed in colorectal carcinoma and prostate cancer, suggesting its potential as both a biomarker and an immunotherapy target in these malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In anaplastic large cell lymphoma, oncogenic signaling (via NPM–ALK and STAT3) induces both miR‐135b and its host gene LEMD1, implying a role for LEMD1 in lymphomagenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in oral squamous cell carcinoma (OSCC), elevated LEMD1 expression correlates with tumor progression, nodal metastasis and poor prognosis, and its knockdown reduces cellular invasion and the ability of malignant cells to adhere to endothelial layers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In colorectal cancer, LEMD1 is preferentially expressed in cancer stem cells, where it appears to contribute to the maintenance of stemness, while in colon cancer models LEMD1 is transcriptionally induced by SOX4 to activate the PI3K/AKT signaling cascade, thereby promoting proliferation, migration, invasion, and angiogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " In gastric and pancreatic cancers, similar pro‐tumorigenic roles have been attributed to LEMD1 through activation of PI3K/AKT and mTORC1 signaling pathways as well as suppression of p53‐dependent tumor responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, increased LEMD1 expression in thyroid cancer has been associated with a higher risk of lymph node metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its oncogenic roles, LEMD1 is also expressed during spermiogenesis, where its nucleoplasmic localization (in contrast to the peripheral distribution of most LEM proteins in somatic cells) suggests a specialized function in nuclear remodeling during germ cell maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these findings indicate that LEMD1 functions as a multifaceted regulator in cancer by promoting tumor cell proliferation, invasion, metastasis and maintaining cancer stem cell properties, while also holding promise as a diagnostic biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daisuke Yuki, Yu-Min Lin, Yoshitaka Fujii, et al. 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