This data suggested that the reduction of integrin β1 expression on cell surface was probably due to post-transcriptional mechanism. Protein glycosylation is an important event for post-transcriptional regulation that contributes to protein maturity. Integrin β1 subunit is a transmembrane glycoprotein. Intriguingly, the β1 integrin may be well positioned for regulation by glycosylation. Unlike other integrin subunits, partially glycosylated β1 integrin precursors also form a stable pool within the endoplasmic

reticulum [33–36]. The cell, therefore, may be able to direct the expression of a variant glycosylated species by recruiting precursors from the ER. How the β1 integrin traffics from ER to Golgi is still unclear. However, this transition indicates a potential target for regulation of β1 integrin expression on cell surface. Our findings in Fig 5A showed that total amount of β1 subunit selleck chemical in Nm23/H7721 cells did not change, which was consistent with the results obtained by RT-PCR. But, the level of mature integrin isoform was decreased significantly, while the level of partially glycosylated precursor was increased. It suggests

that the expression of Nm23-H1 affects the glycosylation see more of integrin β1 precursor and the altered glycosylation of integrin β1 may contribute to the loss of cell surface integrin β1 in Nm23/H7721 cells. In previous studies by others, it was demonstrated that Nm23-H1 could down regulate the transcription of many glycosyltransferase genes, including GnT-V, α1,3FucTs and ST3Gals and that they were correlated with anti-metastasis effect in tumor cells [15, 37]. Accumulating evidence indicates that β1 integrin is an important target for GnT-V and ST6Gal. Therefore, it may be concluded that transfection

of Nm23-H1 cDNA down regulates some key glycosyltransferase genes and then interferes the protein post-translational modification. In consequence, the glycosylation of β1 integrin precursor is impaired, leading to the loss of cell surface β1 tuclazepam integrin. However, the detailed mechanisms need to be further investigated. The mechanisms of regulating integrin-stimulated cell migration are very complex and the activation of tyrosine kinases plays an important role in these events [4]. Emerging evidence supports the important role of FAK PTK in these processes. FAK activation has been linked to integrin clustering and is considered as a critical step in the initiation of cell migration. In cultured cells, overexpression of FAK can increase Fn-stimulated cell motility and this activity depends upon the integrity of the FAK Tyr-397 autophosphorylation site [38, 39]. Our result showed that Nm23-H1 seemed to have no effect on the expression of FAK in H7721 cells, while it decreased the tyrosine phosphorylation of FAK, an important event in integrin-mediated signaling.

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