Autocrine motility factor stimulates the invasiveness of malignant cells as well as up-regulation of matrix metalloproteinase-3 expression via a MAPK pathway

Haga, Arayo; Funasaka, Tatsuyoshi; Deyashiki, Yoshihiro; Raz, Avraham

doi:10.1016/j.febslet.2008.05.005

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Volume 582, Issue 13 , Pages 1877-1882, 11 June 2008

Autocrine motility factor stimulates the invasiveness of malignant cells as well as up-regulation of matrix metalloproteinase-3 expression via a MAPK pathway

Edited by Veli-Pekka Lehto

Arayo Haga
- Gifu Prefectural Research Institute for Health and Environmental Science, 1-1, Naka-Fudougaoka, Kakamigahara 504-0838, Japan
- Department of Hygeinics, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan
- Corresponding author. Address: Gifu Prefectural Research Institute for Health and Environmental Science, 1-1, Naka-Fudougaoka, Kakamigahara 504-0838, Japan. Fax: +81 58 371 5016.
Tatsuyoshi Funasaka
- Department of Hygeinics, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan
- Oncology, Pathology and Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, 110 East Warren, Detroit, MI 48210, USA
Yoshihiro Deyashiki
- Gifu Prefectural Research Institute for Health and Environmental Science, 1-1, Naka-Fudougaoka, Kakamigahara 504-0838, Japan
Avraham Raz
- Oncology, Pathology and Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, 110 East Warren, Detroit, MI 48210, USA

Received 26 February 2008; received in revised form 16 April 2008; accepted 6 May 2008. published online 15 May 2008.

Abstract

The autocrine motility factor (AMF) is a multifunctional protein that is involved in tumor progression including enhanced invasiveness via induction of matrix metalloproteinase-3 (MMP3). The increase in MMP3 was found in an AMF-high production tumor cell line, and c-Jun, c-Fos and mitogen-activated protein kinases (MAPKs) were also highly phosphorylated compared with the parent line. AMF stimulation induced the rapid phosphorylation of the cellular MAPK cascade and MMP3 secretion, which was blocked using a specific MAPK inhibitor. Results of this study suggest that AMF stimulation stimulates MMP3 expression via a MAPK signaling pathway.

Abbreviations: AMF, autocrine motility factor, AMFR, Autocrine motility factor receptor, gp78, 78kDa glyco protein, MMP3, matrix metalloproteinase-3, MAPK, mitogen-activated protein kinase, JNK, c-Jun N-terminal kinase, ERK, extracellular signal-regulated kinases, PKC, protein kinase C, PI3K, phosphatidylinositol 3-kinase, AP-1, activating protein-1, TRE, TPA response element