Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer

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Abstract

Objective: Spheroid colony formation is a useful method of cancer stem cell (CSC) characterization. We previously showed that the IQ motif containing the GTPase-activating protein 3 gene (IQGAP3) is upregulated in spheroid body-forming gastric cancer (GC) cells compared with parental cells. We investigated IQGAP3 expression in GC. Methods: IQGAP3 protein expression was analyzed by immunohistochemistry in 165 GC cases. RNA interference was used to inhibit IQGAP3 expression in GC cell lines. Results: In non neoplastic gastric mucosa, weak staining of IQGAP3 was observed in the foveolar epithelium, while GC tissue showed stronger, more extensive staining. Of the 165 GC cases, 34 (21%) were positive for IQGAP3 expression. GC cases positive for IQGAP3 were found more frequently in stage II/III/IV cases than in stage I cases. Univariate and multivariate analyses demonstrated that IQGAP3 expression is an independent prognostic classifier of GC patients. Both the number and size of the spheres formed by MKN-74 cells were significantly reduced by knockdown of IQGAP3. The phosphorylation of Akt and Erk1/2 was inhibited by knockdown of IQGAP3. Conclusion: These results suggest that IQGAP3 plays an important role in gastric CSCs. The location of IQGAP3 on the cell membrane makes it a potential therapeutic target for GC.

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Author and article information

Journal

Journal ID (publisher-id): PAT

Journal ID (nlm-ta): Pathobiology

Journal ID (doi): 10.1159/issn.1015-2008

Title: Pathobiology

Publisher: S. Karger AG

ISSN (Print): 1015-2008

ISSN (Electronic): 1423-0291

Publication date Subscription-year: 2018

Publication date (Print): May 2018

Publication date (Electronic): 01 November 2017

Volume: 85

Issue: 3

Pages: 192-200

Affiliations

[_a] _aDepartment of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

[_b] _bDepartment of Surgery, Yokohama City University, Yokohama, Japan

[_c] _cDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Author notes

*Naohide Oue, Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan), E-Mail naoue@hiroshima-u.ac.jp

Article

Publisher ID: 481890 Other ID: Pathobiology 2018;85:192–200

DOI: 10.1159/000481890

PubMed ID: 29131081

SO-VID: 473fd88f-a307-4334-9262-4b6b96767b54

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 26 July 2017

Date accepted : 02 October 2017

Page count

Figures: 2, Tables: 3, Pages: 9

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