Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1

Sep 21, 2026

Uploaded by Riley

Recent studies indicate transmembrane tight junction proteins are elevated in cancers and may drive tumor progression, making them potential therapeutic targets. This work demonstrates distinct expression patterns and a new function for junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry links high JAM-A to carcinoma in situ and higher invasive carcinoma expression, correlating with lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A modulates proliferation and migration. Multilayered proteomics shows JAM-A interacts with LAT1, regulates LAT1 expression on the whole-cell membrane, and enhances amino acid uptake to promote tumor growth; combined high JAM-A and LAT1 predicts poor prognosis, and an extracellular JAM-A antibody suppresses proliferation.

LanguageEnglish

CategoryResearch & Report

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Pages16

Reading Time40 min

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Abstract

Expression and clinical associations of JAM-A in breast cancer

Cellular effects: proliferation and migration

Proteomics mechanism: JAM-A–LAT1 interaction and amino acid uptake

Therapeutic implication and prognosis markers

Received: 12 December 2023 Revised: 6 June 2024 Accepted: 16 June 2024 DOI: 10. 1111/cas.16259 OR I G I NAL ART I C L E Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1 Kazufumi Magara1 | Akira Takasawa1,2 | Kumi Takasawa1,2 | Tomoyuki Aoyama1 | Misaki Ota1,3 | Daisuke Kyuno1,4 | Yusuke Ono1 | Taro Murakami1 | Soh Yamamoto5 | Yuna Nakamori1,6 | Naoya Nakahashi1,7 | Goro Kutomi4 | Ichiro Takemasa4 | Tadashi Hasegawa8 | Makoto Osanai1 1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan 2Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan 3 Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan 4Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan 5Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan 6Department of Oral Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan 7Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan 8 Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan Correspondence Akira Takasawa, Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, 2-1- 1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078-8510, Japan. Email: [atakasawa@asahikawa-med.ac.jp](atakasawa@asahikawa-med.ac.jp) Funding information Japan Society for the Promotion of Science, Grant/Award Number: JP22J15489 Abstract Recent studies have shown that transmembrane-type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM-A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM-A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM-A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM-A 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-A and LAT1 predicts poor prognosis in patients with breast Abbreviations: AP-MS, affinity purification mass spectrometry; BC, breast cancer; BPA, boronophenylalanine; coIP-MS, co-immunoprecipitation-mass spectrometry; DAVID, database for annotation, visualization, and integrated discovery; DCIS, ductal carcinoma in situ; DE, ductal epithelium; GO, gene ontology; JAM-A, junctional adhesion molecule-A; KEGG, Kyoto Encyclopedia of Genes and Genomes; IDC, invasive ductal carcinoma; IRS, immunoreactivity score; IP, immunoprecipitation; LAT1, large neutral amino acids transporter small subunit 1; MiST, mass spectrometry interaction statistics; MS, mass spectrometry; MS/MS, tandem mass spectrometry; NPM3, nucleoplasmin-3; PPI, protein–protein interaction; RCN1, reticulocalbin 1; TJ, tight junction; TJP, tight junction protein. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s) . Cancer Science published by John Wiley & Sons Australia, Ltd

FAQs

What does the study show about JAM-A expression in breast cancer tissues?

JAM-A is highly expressed from carcinoma in situ lesions and shows higher expression in invasive carcinomas compared with other adenocarcinomas.

How does JAM-A affect breast cancer cell behavior?

JAM-A expression status influences malignant potentials including proliferation and migration in breast cancer cells.

What mechanism links JAM-A to tumor growth according to the proteomics results?

Multilayered proteomics indicates JAM-A interacts with LAT1, regulates LAT1 expression, and promotes enhanced amino acid uptake by facilitating LAT1 activity at the whole cell membrane, thereby supporting tumor growth.

Sep 21, 2026

Uploaded by Riley