Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes

Takuya Shirakihara, Tomonori Kawasaki, Akihiko Fukagawa, Kentaro Senba, Ryuichi Sakai, Kohei Miyazono, Keiji Miyazawa, Masao Saitoh

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    Epithelial-mesenchymal transition (EMT) is a crucial event in wound healing, tissue repair, and cancer progression in adult tissues. Transforming growth factor (TGF)-β induces EMT in mouse epithelial cells. During prolonged treatment, TGF-β successively induces myofibroblastic differentiation with increased expression of myofibroblast marker proteins, including smooth muscle α actin and calponin. We recently showed that fibroblast growth factor-2 prevented myofibroblastic differentiation induced by TGF-β, and transdifferentiated the cells to those with much more aggressive characteristics (enhanced EMT). To identify the molecular markers specifically expressed in cells undergoing enhanced EMT induced by the combination of TGF-β and fibroblast growth factor-2, we carried out a microarray-based analysis and found that integrin α3 (ITGA3) and Ret were upregulated. Intriguingly, ITGA3 was also overexpressed in breast cancer cells with aggressive phenotypes and its expression was correlated with that of δEF-1, a key regulator of EMT. Moreover, the expression of both genes was downregulated by U0126, a MEK 1/2 inhibitor. Therefore, ITGA3 is a potential marker protein for cells undergoing enhanced EMT and for cancer cells with aggressive phenotypes, which is positively regulated by δEF-1 and the MEK-ERK pathway.

    Original languageEnglish
    Pages (from-to)1189-1197
    Number of pages9
    JournalCancer Science
    Volume104
    Issue number9
    DOIs
    Publication statusPublished - 2013 Sep

    Fingerprint

    Epithelial-Mesenchymal Transition
    Integrins
    Transforming Growth Factors
    Phenotype
    Peptide Elongation Factor 1
    Neoplasms
    Fibroblast Growth Factor 2
    Myofibroblasts
    MAP Kinase Signaling System
    Mitogen-Activated Protein Kinase Kinases
    Microarray Analysis
    Wound Healing
    Smooth Muscle
    Actins
    Proteins
    Down-Regulation
    Epithelial Cells
    Breast Neoplasms
    Gene Expression

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. / Shirakihara, Takuya; Kawasaki, Tomonori; Fukagawa, Akihiko; Senba, Kentaro; Sakai, Ryuichi; Miyazono, Kohei; Miyazawa, Keiji; Saitoh, Masao.

    In: Cancer Science, Vol. 104, No. 9, 09.2013, p. 1189-1197.

    Research output: Contribution to journalArticle

    Shirakihara, Takuya ; Kawasaki, Tomonori ; Fukagawa, Akihiko ; Senba, Kentaro ; Sakai, Ryuichi ; Miyazono, Kohei ; Miyazawa, Keiji ; Saitoh, Masao. / Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. In: Cancer Science. 2013 ; Vol. 104, No. 9. pp. 1189-1197.
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