Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells.

التفاصيل البيبلوغرافية
العنوان:	Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells.
المؤلفون:	Tominaga K; Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; ngotoh@staff.kanazawa-u.ac.jp k.n.tominga22@gmail.com.; Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan.; Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa City, Ishikawa 920-1192, Japan., Minato H; Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Uchinada-Machi, Ishikawa 920-0265, Japan., Murayama T; Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan., Sasahara A; Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Nishimura T; Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa City, Ishikawa 920-1192, Japan., Kiyokawa E; Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Uchinada-Machi, Ishikawa 920-0265, Japan., Kanauchi H; Department of Breast and Endocrine Surgery, Showa General Hospital, Kodaira City, Tokyo 187-8510, Japan., Shimizu S; Department of Pathological Diagnosis, Showa General Hospital, Kodaira City, Tokyo 187-8510, Japan., Sato A; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Nishioka K; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Tsuji EI; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Yano M; Department of Surgery, Minami-Machida Hospital, Machida City, Tokyo 194-0004, Japan., Ogawa T; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Ishii H; Department of Medical Data Science, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan., Mori M; Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan., Akashi K; Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan., Okamoto K; Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan., Tanabe M; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Tada KI; Department of Breast and Endocrine Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 112-8655, Japan., Tojo A; Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan., Gotoh N; Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; ngotoh@staff.kanazawa-u.ac.jp k.n.tominga22@gmail.com.; Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa City, Ishikawa 920-1192, Japan.
المصدر:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jan 08; Vol. 116 (2), pp. 625-630. Date of Electronic Publication: 2018 Dec 26.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH:	Cell Division* , Signal Transduction, Breast Neoplasms/metabolism , Mixed Function Oxygenases/metabolism , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/metabolism , Semaphorin-3A/metabolism, Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Gene Knockdown Techniques ; Humans ; Mice ; Mixed Function Oxygenases/genetics ; Neoplasm Proteins/genetics ; Neoplastic Stem Cells/pathology ; Semaphorin-3A/genetics ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology
مستخلص:	Cancer stem-like cells (CSCs) are expanded in the CSC niche by increased frequency of symmetric cell divisions at the expense of asymmetric cell divisions. The symmetric division of CSCs is important for the malignant properties of cancer; however, underlying molecular mechanisms remain largely elusive. Here, we show a cytokine, semaphorin 3 (Sema3), produced from the CSC niche, induces symmetric divisions of CSCs to expand the CSC population. Our findings indicate that stimulation with Sema3 induced sphere formation in breast cancer cells through neuropilin 1 (NP1) receptor that was specifically expressed in breast CSCs (BCSCs). Knockdown of MICAL3 , a cytoplasmic Sema3 signal transducer, greatly decreased tumor sphere formation and tumor-initiating activity. Mechanistically, Sema3 induced interaction among MICAL3, collapsin response mediator protein 2 (CRMP2), and Numb. It appears that activity of MICAL3 monooxygenase (MO) stimulated by Sema3 is required for tumor sphere formation, interaction between CRMP2 and Numb, and accumulation of Numb protein. We found that knockdown of CRMP2 or Numb significantly decreased tumor sphere formation. Moreover, MICAL3 knockdown significantly decreased Sema3-induced symmetric divisions in NP1/Numb-positive BCSCs and increased asymmetric division that produces NP1/Numb negative cells without stem-like properties. In addition, breast cancer patients with NP1-positive cancer tissues show poor prognosis. Therefore, the niche factor Sema3-stimulated NP1/MICAL3/CRMP2/Numb axis appears to expand CSCs at least partly through increased frequency of MICAL3-mediated symmetric division of CSCs. Competing Interests: Conflict of interest statement: N.G., K.T., and A.T. applied for patent pending (2015-132122) in Japan. (Copyright © 2019 the Author(s). Published by PNAS.)
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فهرسة مساهمة:	Keywords: breast cancer; cancer stem cell niche; neuropilin; semaphorin; tumor micoenvironment
المشرفين على المادة:	0 (Neoplasm Proteins) 0 (SEMA3A protein, human) 0 (Semaphorin-3A) EC 1.- (MICAL3 protein, human) EC 1.- (Mixed Function Oxygenases)
تواريخ الأحداث:	Date Created: 20181228 Date Completed: 20190312 Latest Revision: 20200309
رمز التحديث:	20231215
مُعرف محوري في PubMed:	PMC6329980
DOI:	10.1073/pnas.1806851116
PMID:	30587593
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1091-6490
DOI:	10.1073/pnas.1806851116