Reduced paxillin expression contributes to the antimetastatic effect of 4-hydroxycoumarin on B16-F10 melanoma cells

Abstract

Background: 4-Hydroxycoumarin (4-HC) is a coumarin that lacks anticoagulant activity. 4-HC affects the cytoskeletal stability and decreases cell adhesion and motility of the melanoma cell line B16-F10. Together with integrins and other cytoskeletal proteins, paxillin participates in the regulation of cell adhesion and motility, acting as an adapter protein at focal adhesions. The present study determined the participation of paxillin in the reported effects of 4-HC and analyzed the role of paxillin in the formation of melanoma metastases.

MDA-9/Syntenin Is Essential for Factor VIIa-induced Signaling, Migration, and Metastasis in Melanoma Cells

“…Interestingly, our results demonstrated that the PDZ scaffold protein MDA-9/syntenin forms a signaling complex with Src that requires exogeneous rFVIIa and FX. We observed that inhibition of the MDA-9/syntenin interactions with c-Src blocked TF⅐FVIIa⅐Xa/PAR-1-induced Rac-1/Cdc42 and JNK signaling and that inhibiting JNK prevented TF⅐ FVIIa⅐Xa/PAR- , three major JNK phosphorylation sites that facilitate tumor cell migration and metastatic spread of several human malignancies (36,37,45). These observations coupled with our present findings suggest that the MDA-9⅐syntenin⅐c-Src signaling complex induced by a TF⅐ FVIIa⅐Xa pathway most likely facilitates tumor cells to leave their original tumor site and migrate to the lungs.…”

“…Overall, these finding and our present study suggest a series of coordinated signaling transduction events involving MDA-9/syntenin that ultimately leads to the acquisition of a motile phenotype by melanoma cells. Indeed, blocking MDA-9/syntenin in response to rFVIIa and FX, or interfering with TF (48), Rho proteins (49), NF-B-regulated genes such as MMP-2 (50), or more importantly inhibition of the Src/paxillin signaling pathway (45,51) has been shown to inhibit tumor growth and metastasis in preclinical studies and clinical trials.…”

FAK and paxillin, two potential targets in pancreatic cancer

“…Paxillin is known to acquire gain of function mutations that are associated with alterations in the malignant progression of many tumors [ 81 – 83 ] including breast, lung [ 84 – 86 ], prostate [ 87 ], melanoma [ 88 ] and colorectal cancer [ 89 ]. The most common mutation, A128T as identified from our laboratory, is linked to invasive tumor growth [ 79 , 84 , 90 – 92 ].…”

Hic‐5 affects proliferation, migration and invasion of B16 murine melanoma cells

“…Furthermore, survival rates were significantly improved in mice injected with shHic‐5‐1 and shHic‐5‐2 cells compared with mice injected with control cells (Figure 3D). Paxillin, a focal adhesion adaptor protein that shares structural homology with Hic‐5 (Nishiya et al., 2001), has been reported to participate in the adhesion of B16‐F10 melanoma cells to mouse lung tissue (Velasco‐Velazquez et al., 2008). Therefore, we tested whether the down‐regulation of Hic‐5 would affect B16‐F1 adhesion on planar collagen IV matrix.…”