The suppressor of metastasis Nm23-H1 interacts with the Cdc42 Rho family member and the pleckstrin homology domain of oncoprotein Dbl-1 to suppress cell migration.

Cancer Biology & Therapy
Masanao MurakamiErle S Robertson

Abstract

Tumor invasion and metastasis is regulated by a number of cellular molecules known to be involved in signaling and cytoskeletal rearrangement. One of these molecules is the suppressor of tumor metastasis Nm23-H1 which linked to invasiveness and metastatic potential of human cancers. Nm23-H1 expression is down-regulated in human melanoma and invasive breast carcinoma. Recent studies have shown an association between the Nm23-H1 and oncoprotein Dbl-1 which is associated with guanine exchange and belongs to a family of Guanine Exchange Factors (GEF). In this report we show a direct interaction in vitro and in human B cells and specifically identified the pleckstrin homology domain of Dbl-1 as the domain which binds to Nm23-H1. Furthermore, Nm23-H1 and Dbl-1 colocalized in the cytoplasm of COS-7 cells when expressed exogenously and showed predominant signals at the periphery of the cells particularly at the plasma membrane. Interestingly, Dbl-1 and Cdc42 expression rescued the suppressive activities of Nm23-H1 in cell migration assays. We show that Cdc42 a regulatory protein involved in cytoskeletal reorganization, cell growth and development can bind to Nm23-H1 and the kinase deficient mutant H118F but only weakly to the mutant P9...Continue Reading

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