{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNECTIN3 is a member of the nectin family of cell adhesion molecules that orchestrate the formation of adherens and tight junctions. Alterations in its expression have been observed in diverse pathological states, including endometriosis, where immunostaining studies have revealed modified patterns of nectins and related molecules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the immune system, NECTIN3 (also known as CD113) is uniquely expressed by T lymphocytes, where it engages in trans‐interactions with NECTIN2 on endothelial cells. This interaction is critical for lymphocyte transendothelial migration and extravasation during immune surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In parallel, studies in pancreatic cancer further underscore the importance of nectins in cell–cell adhesion; aberrant expression of these molecules is implicated in promoting metastasis and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNECTIN3 also functions as a cellular receptor for bacterial toxins. Gene-trap and mutagenesis studies have identified PVRL3 (the gene encoding NECTIN3) as a necessary binding partner for Clostridium difficile toxin B. Loss or disruption of NECTIN3 expression confers resistance to toxin-mediated cytotoxicity, highlighting its role in bacterial pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn reproductive biology, nectins are vital for maintaining the specialized junctional contacts between Sertoli cells and germ cells. Experimental mouse models in which NECTIN3 is disrupted present with severe spermiogenic defects—including abnormal sperm morphology, reduced motility, and impaired fertilizing capability—illustrating its essential role in spermatogenesis and male fertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer contexts, the function of NECTIN3 appears to be cell type– and context-dependent. In ovarian cancer, high levels of NECTIN3 expression are associated with increased matrix metallopeptidase (MMP2/MMP9) expression, enhanced cellular migration and invasion, and poorer overall survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Conversely, in pancreatic neuroendocrine tumors, reduced membranous expression of NECTIN3 correlates with features of aggressive disease. These findings suggest that both the level and subcellular distribution of NECTIN3 can influence tumor progression and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marcos Ballester, Julie Gonin, Anita Rodenas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/des304"}], "href": "https://doi.org/10.1093/humrep/des304"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22926846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22926846"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elisabeth Devilard, Luc Xerri, Patrice Dubreuil, et al. 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