RECKing MMP: Relevance of Reversion-inducing Cysteine-rich Protein with Kazal Motifs as a Prognostic Marker and Therapeutic Target for Cancer (A Review)

Siddavaram      Nagini

doi:10.2174/187152012802650237

Abstract

Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is a membrane-anchored glycoprotein that negatively regulates the activities of matrix metalloproteinases (MMPs) and inhibits tumor invasion, metastasis, and angiogenesis. RECK is essential for normal development and is a key mediator of tissue remodeling and stabilization of tissue architechture. Downregulation of RECK documented in a wide range of malignant neoplasms correlates with poor prognosis, and tumor metastasis. The RECK gene is a common negative target for oncogenic signals that act on the Sp1-binding site of the RECK promoter. Both natural and synthetic agents have been identified as upregulators of RECK. Several strategies have been proposed to enhance RECK expression including forced expression of RECK, use of mimetics, recombinant peptides, microRNA antagonists, and gene therapy. Upregulation of RECK could be a valuable therapeutic option to improve prognosis and block tumor progression. This review addresses the potential value of RECK as a prognostic marker and as a molecular target for cancer therapy.

Keywords: Angiogenesis, Histone deacetylase, Invasion, Matrix metalloproteinases, RECK, Sp1 protein, Tissue inhibitor of matrix metalloproteinases, cytotrophoblasts, syncytiotrophoblasts, glycosylphosphatidylinositol.