{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMUCL1, originally discovered as small breast epithelial mucin (SBEM), is a glycoprotein with highly restricted expression in mammary tissue that has attracted attention as a diagnostic biomarker in breast cancer. Its expression has been linked to clinical parameters such as tumor node metastasis, lymph node involvement, and response to neoadjuvant chemotherapy, as well as serving as a sensitive molecular indicator of hematogenous and bone marrow micrometastasis. In addition, promoter studies have revealed that tissue‐selective transcription factors (e.g. octamer‐binding proteins) drive its strong and breast‐specific expression, further underlining its potential utility in early detection strategies for this disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies in breast cancer cells have demonstrated that MUCL1 plays a pivotal role in modulating tumor cell behavior. In HER2‐amplified tumors, its expression is regulated via the phosphoinositide3‐kinase/Akt pathway and impacts cell cycle progression—its knockdown induces G1/S arrest accompanied by reduced cyclin D levels and increased p21/p27. MUCL1 also enhances cellular migration and invasion by promoting epithelial‐to‐mesenchymal transition; its overexpression correlates with increased levels of mesenchymal markers and activation of the FAK/JNK cascade. Moreover, in colorectal cancer, MUCL1 exerts oncogenic effects by enhancing proliferation, colony formation, and by driving β‐catenin activation through specific phosphorylation events, while the broader protective roles of mucins in epithelial tissues (such as skin) underscore its diverse biological functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have further illustrated that alterations in microRNA expression can modulate MUCL1 levels in breast cancer. In particular, low expression of miR‑186‑5p has been shown to result in abnormally high MUCL1 expression, which in turn activates the PI3K/AKT signaling cascade and drives enhanced migratory and invasive behavior of cancer cells. These findings support the notion that therapeutic strategies aimed at targeting MUCL1, either directly or via its regulatory microRNAs, may offer new avenues for treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "F Hubé, M Mutawe, E Leygue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human small breast epithelial mucin: the promise of a new breast tumor biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2004.23.842"}], "href": "https://doi.org/10.1089/dna.2004.23.842"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15684711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15684711"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Florent Hubé, Shilpa Chooniedass-Kothari, Mohammad K Hamedani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an octamer-binding site controlling the activity of the small breast epithelial mucin gene promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Biosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2741/1984"}], "href": "https://doi.org/10.2741/1984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16720387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16720387"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "G P Skliris, F Hubé, I Gheorghiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of small breast epithelial mucin (SBEM) protein in tissue microarrays (TMAs) of primary invasive breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histopathology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2559.2007.02955.x"}], "href": "https://doi.org/10.1111/j.1365-2559.2007.02955.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18269587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18269587"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Manuel Valladares Ayerbes, Silvia Díaz-Prado, Daniel Ayude, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In silico and in vitro analysis of small breast epithelial mucin as a marker for bone marrow micrometastasis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-0-387-69080-3_31"}], "href": "https://doi.org/10.1007/978-0-387-69080-3_31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18497056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18497056"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Manuel Valladares-Ayerbes, Pilar Iglesias-Díaz, Silvia Díaz-Prado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diagnostic accuracy of small breast epithelial mucin mRNA as a marker for bone marrow micrometastasis in breast cancer: a pilot study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-009-0559-7"}], "href": "https://doi.org/10.1007/s00432-009-0559-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19221791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19221791"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhao-Zhe Liu, Xiao-Dong Xie, Shu-Xian Qu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10585-010-9323-2"}], "href": "https://doi.org/10.1007/s10585-010-9323-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20364301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20364301"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "S J Conley, E E Bosco, D A Tice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HER2 drives Mucin-like 1 to control proliferation in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.487"}], "href": "https://doi.org/10.1038/onc.2015.487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26725324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26725324"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qiu-Hua Li, Zhao-Zhe Liu, Ya-Νan Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial‑to‑mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2020.7640"}], "href": "https://doi.org/10.3892/or.2020.7640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32627029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32627029"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "J Kim, H Choi "}, {"type": "b", "children": [{"type": "t", "text": "The mucin protein MUCL1 regulates melanogenesis and melanoma genes in a manner dependent on threonine content."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Dermatol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjd.20761"}], "href": "https://doi.org/10.1111/bjd.20761"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34545566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34545566"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Maha Abdulla, Thamer Bin Traiki, Mansoor-Ali Vaali-Mohammed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2022.5312"}], "href": "https://doi.org/10.3892/ijo.2022.5312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35059735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35059735"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hui Hao, Bingsheng Wang, Lin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNA-186-5p inhibits migration, invasion and proliferation of breast cancer cells by targeting SBEM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.204887"}], "href": "https://doi.org/10.18632/aging.204887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37477531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37477531"}]}]}]}