This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-09-0488v1 69/13/5349    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Funasaka, T. Articles by Raz, A. PubMed PubMed Citation Articles by Funasaka, T. Articles by Raz, A.

Phosphoglucose Isomerase/Autocrine Motility Factor Mediates Epithelial and Mesenchymal Phenotype Conversions in Breast Cancer

Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, Michigan

Requests for reprints: Avraham Raz, Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, School of Medicine, 110 East Warren Avenue, Detroit, MI 48201. Phone: 313-833-0960; Fax: 313-831-7518; E-mail: raza{at}karmanos.org.

Key Words: AMF/PGI • EMT • MET

Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is a housekeeping gene product/cytokine that catalyzes a step in glycolysis and gluconeogenesis, and acts as a multifunctional cytokine associated with aggressive tumors. PGI/AMF has been correlated significantly with breast cancer progression and poor prognosis in breast cancer. We show here that ectopic expression of PGI/AMF induced epithelial-to-mesenchymal transition (EMT) in MCF10A normal human breast epithelial cells, and inhibition of PGI/AMF expression triggered mesenchymal-to-epithelial transition (MET) in aggressive mesenchymal-type human breast cancer MDA-MB-231 cells. EMT in MCF10A cells was shown by morphologic changes and loss of E-cadherin/β-catenin–mediated cell-cell adhesion, which is concomitant with the induction of the E-cadherin transcriptional repressor Snail and proteosome-dependent degradation of β-catenin protein. Molecular analysis showed that PGI/AMF suppressed epithelial marker expressions and enhanced mesenchymal marker expressions. Silencing of PGI/AMF expression by RNA interference in MDA-MB-231 cells induced the reverse processes of EMT including altered cell shape, gain of epithelial marker, and reduction of mesenchymal marker, e.g., MET. Taken together, the results show the involvement of PGI/AMF in both EMT and MET: overexpression of PGI/AMF induces EMT in normal breast epithelial cells and reduction of PGI/AMF expression led to MET in aggressive breast cancer cells. These results suggest for the first time that PGI/AMF is a key gene to both EMT in the initiating step of cancer metastasis and MET in the later stage of metastasis during breast cancer progression. [Cancer Res 2009;69(13):5349–56]