{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:06:32Z","timestamp":1762459592740,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T00:00:00Z","timestamp":1525392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672747","31560323","81272356","81330029"],"award-info":[{"award-number":["81672747","31560323","81272356","81330029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The human rhomboid family (RHBDF)1 gene is highly expressed in breast cancer under clinical conditions but not in normal mammary gland tissues. Silencing the RHBDF1 gene in breast cancer xenograft tumors leads to inhibition of tumor growth. We show in this study that artificially raising RHBDF1 protein levels in the mammary epithelial cells MCF\u201010A results in severe perturbations of the ability of the cells to form lumencontaining acini, either in 3\u2010dimensional cell cultures or implanted in mouse mammary fat pads. Knocking down RHBDF1 with short hairpin (sh)RNA leads to restoration of acinus formation. Consistently, RHBDF1 overexpression gives rise to disordered distribution of polarity markers GM130 and laminin\u20105, which otherwise are located in apical and basal positions, respectively, in the acini. Further investigations reveal that RHBDF1 directly binds to Par6a, a component of a protein complex consisting of partitioning\u2010defective scaffold protein (Par)6, Par3, renin\u2010angiotensin system\u2010related C3 botulinum toxin substrate (Rac)1, and cell\u2010 division cycle (Cdc)42, which is structurally critical to the formation of apicobasal polarity. RHBDF1 binding to Par6a results in collapse of the protein complex and thus disruption of polarity formation. Since early stages of breast cancer are characterized by the loss of mammary gland epithelial cell polarity, our findings indicate that perturbations of apicobasal polarity by high levels of RHBDF1 is a significant attribute in the development of breast neoplasia.\u2014Peng, X.\u2010M., Gao, S., Deng, H.\u2010T., Cai, H.\u2010X., Zhou, Z., Xiang, R., Zhang, Q.\u2010Z., Li, L.\u2010Y. Perturbation of epithelial apicobasal polarity by rhomboid family\u20101 gene overexpression.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 5577\u20135586 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800016r","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T13:29:02Z","timestamp":1525440542000},"page":"5577-5586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Perturbation of epithelial apicobasal polarity by rhomboid family\u20101 gene overexpression"],"prefix":"10.1096","volume":"32","author":[{"given":"Xue\u2010Mei","family":"Peng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology College of Pharmacy, Tianjin Key Laboratory of 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