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Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule\u2010A (JAM\u2010A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM\u2010A was highly expressed from carcinoma in\u00a0situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM\u2010A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM\u2010A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM\u2010A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM\u2010A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM\u2010A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM\u2010A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM\u2010A\u2010targeted therapy ideally combined with LAT1\u2010targeted therapy as a new therapeutic strategy against breast cancer.<\/jats:p>","DOI":"10.1111\/cas.16259","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T10:44:02Z","timestamp":1719657842000},"page":"3153-3168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multilayered proteomics reveals that <scp>JAM<\/scp>\u2010A promotes breast cancer progression via regulation of amino acid transporter <scp>LAT1<\/scp>"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-6011","authenticated-orcid":false,"given":"Kazufumi","family":"Magara","sequence":"first","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine  Sapporo 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