دورية أكاديمية
أعرض في EDS

Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair.

التفاصيل البيبلوغرافية
العنوان: Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair.
المؤلفون: Matsuo J; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Douchi D; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan., Myint K; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Mon NN; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Yamamura A; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan., Kohu K; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Heng DL; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Chen S; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Mawan NA; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Nuttonmanit N; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Li Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Srivastava S; Department of Medicine, National University of Singapore, Singapore., Ho SWT; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore., Lee NYS; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore., Lee HK; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore., Adachi M; Graduate School of Medicine, Kyoto University, Kyoto, Japan., Tamura A; Department of Pharmacology, School of Medicine, Teikyo University, Tokyo, Japan.; Strategic Innovation and Research Center, Teikyo University, Tokyo, Japan.; Laboratory of Barriology and Cell Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan., Chen J; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore., Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Teh M; Department of Pathology, National University of Singapore, Singapore., So JB; Department of Surgery, National University Health System, National University of Singapore, Singapore., Yong WP; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Department of Hematology-Oncology, National University Cancer Institute, Singapore., Tan P; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore.; Genome Institute of Singapore, Singapore., Yeoh KG; Department of Medicine, National University of Singapore, Singapore.; Department of Gastroenterology and Hepatology, National University Hospital, Singapore., Chuang LSH; Cancer Science Institute of Singapore, National University of Singapore, Singapore csiitoy@nus.edu.sg atsukita@biosci.med.osaka-u.ac.jp csicshl@nus.edu.sg., Tsukita S; Strategic Innovation and Research Center, Teikyo University, Tokyo, Japan csiitoy@nus.edu.sg atsukita@biosci.med.osaka-u.ac.jp csicshl@nus.edu.sg.; Laboratory of Barriology and Cell Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan., Ito Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore csiitoy@nus.edu.sg atsukita@biosci.med.osaka-u.ac.jp csicshl@nus.edu.sg.
المصدر: Gut [Gut] 2021 Oct; Vol. 70 (10), pp. 1833-1846. Date of Electronic Publication: 2020 Dec 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: British Medical Assn Country of Publication: England NLM ID: 2985108R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3288 (Electronic) Linking ISSN: 00175749 NLM ISO Abbreviation: Gut Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, British Medical Assn.
مواضيع طبية MeSH: GTPase-Activating Proteins/*metabolism , Gastric Mucosa/*cytology , Homeostasis/*physiology , Stem Cells/*cytology , Stomach Neoplasms/*metabolism, Animals ; Biomarkers, Tumor/metabolism ; Cell Proliferation/physiology ; Disease Models, Animal ; Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Stomach Neoplasms/drug therapy ; Tamoxifen/toxicity
مستخلص: Objective: Tissue stem cells are central regulators of organ homoeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus.
Design: We uncovered the specific expression of Iqgap3 in proliferating isthmus stem cells through immunofluorescence and in situ hybridisation. We performed lineage tracing and transcriptomic analysis of Iqgap3 +isthmus stem cells with the Iqgap3-2A-tdTomato mouse model. Depletion of Iqgap3 revealed its functional importance in maintenance and proliferation of stem cells. We further studied Iqgap3 expression and the associated gene expression changes during tissue repair after tamoxifen-induced damage. Immunohistochemistry revealed elevated expression of Iqgap3 in proliferating regions of gastric tumours from patient samples.
Results: Iqgap3 is a highly specific marker of proliferating isthmus stem cells during homoeostasis. Iqgap3+isthmus stem cells give rise to major cell types of the corpus unit. Iqgap3 expression is essential for the maintenance of stem potential. The Ras pathway is a critical partner of Iqgap3 in promoting strong proliferation in isthmus stem cells. The robust induction of Iqgap3 expression following tissue damage indicates an active role for Iqgap3 in tissue regeneration.
Conclusion: IQGAP3 is a major regulator of stomach epithelial tissue homoeostasis and repair. The upregulation of IQGAP3 in gastric cancer suggests that IQGAP3 plays an important role in cancer cell proliferation.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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فهرسة مساهمة: Keywords: cell proliferation; gastric cancer; gastric pre-cancer; gastric wound repair; stem cells
المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (GTPase-Activating Proteins)
0 (IQGAP3 protein, mouse)
094ZI81Y45 (Tamoxifen)
تواريخ الأحداث: Date Created: 20201209 Date Completed: 20220107 Latest Revision: 20220107
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC8458072
DOI: 10.1136/gutjnl-2020-322779
PMID: 33293280
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-3288
DOI:10.1136/gutjnl-2020-322779