Abstract
Metastasis is the primary cause of mortality and morbidity in most cancer patient and accounts for about 90% of cancer death. During the progression of metastasis, the cancer cell motility may determine the initiation process of metastasis. In this study, we investigate the role of a specific GAG-binding peptide (GBP), which possesses cell penetrating activity and interacts with cell surface heparan sulfate proteoglycan (HSPG), on regulating cancer cell motility. To investigate the underlying mechanism of GBP regulated cell migration, we examined focal adhesion and actin dynamics in response to GBP treatment. We found that GBP increased the focal adhesion numbers, length, and stability in A549 cells. In addition, GBP also enhanced cell adhesion, probably mediated by its intracellular function. Notably, we found that GBP changed the intracellular distribution of actin. A transient increase in stress fiber actin and a reduction of actin network was detected upon treatment with GBP. GBP also induced transient phosphorylation of FAK and down-regulation of paxillin. Next, GBP co-localized with two cell surface heparan sulfate proteoglycan, syndecan-1 (SDC-1) and syndecan-4 (SDC-4). Treatment with GBP promoted syndecan-1 internalization. Although direct targets of GBP is not identified in this study, our results indicate that GBP may interfere with dynamic regulations on focal adhesion and actin filaments, and thereby reduced cancer cell migration.