CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells

Eriko Komiya; Kei Ohnuma; Hiroto Yamazaki; Ryo Hatano; Satoshi Iwata; Toshihiro Okamoto; Nam H Dang; Taketo Yamada; Chikao Morimoto

doi:10.1016/j.bbrc.2014.04.037

CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells

Biochem Biophys Res Commun. 2014 May 16;447(4):609-15. doi: 10.1016/j.bbrc.2014.04.037. Epub 2014 Apr 18.

Authors

Eriko Komiya¹, Kei Ohnuma², Hiroto Yamazaki¹, Ryo Hatano¹, Satoshi Iwata¹, Toshihiro Okamoto¹, Nam H Dang³, Taketo Yamada⁴, Chikao Morimoto¹

Affiliations

¹ Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
² Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: [email protected].
³ Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road, Box 100278, Room MSB M410A, Gainesville, FL 32610, USA.
⁴ Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

PMID: 24747072
DOI: 10.1016/j.bbrc.2014.04.037

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.

Keywords: CD26; Malignant pleural mesothelioma; Periostin; Src; Twist1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism*
Cell Line, Tumor
Cell Movement / physiology
Dipeptidyl Peptidase 4 / genetics
Dipeptidyl Peptidase 4 / metabolism*
Gene Knockdown Techniques
Humans
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Mesothelioma / genetics
Mesothelioma / metabolism*
Mesothelioma / pathology*
Mesothelioma, Malignant
Neoplasm Invasiveness / pathology
Neoplasm Invasiveness / physiopathology
Nuclear Proteins / metabolism
Pleural Neoplasms / genetics
Pleural Neoplasms / metabolism*
Pleural Neoplasms / pathology*
Protein Kinase Inhibitors / pharmacology
Pyrimidines / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
RNA, Small Interfering / genetics
Twist-Related Protein 1 / metabolism
Up-Regulation
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / metabolism

Substances

AG 1879
Cell Adhesion Molecules
Nuclear Proteins
POSTN protein, human
Protein Kinase Inhibitors
Pyrimidines
RNA, Messenger
RNA, Neoplasm
RNA, Small Interfering
TWIST1 protein, human
Twist-Related Protein 1
src-Family Kinases
DPP4 protein, human
Dipeptidyl Peptidase 4