Article

ZBP1 enhances cell polarity and reduces chemotaxis

Albert Einstein College of Medicine, New York, New York, United States
Journal of Cell Science (Impact Factor: 5.33). 10/2007; 120(Pt 18):3173-8. DOI: 10.1242/jcs.000638
Source: PubMed

ABSTRACT The interaction of beta-actin mRNA with zipcode-binding protein 1 (ZBP1) is necessary for its localization to the lamellipod of fibroblasts and plays a crucial role in cell polarity and motility. Recently, we have shown that low ZBP1 levels correlate with tumor-cell invasion and metastasis. In order to establish a cause and effect relationship, we expressed ZBP1 in a metastatic rat mammary adenocarcinoma cell line (MTLn3) that has low endogenous ZBP1 levels and delocalized beta-actin mRNA. This leads to localization of beta-actin mRNA, and eventually reduces the chemotactic potential of the cells as well as their ability to move and orient towards vessels in tumors. To determine how ZBP1 leads to these two apparently contradictory aspects of cell behavior--increased cell motility but decreased chemotaxis--we examined cell motility in detail, both in cell culture and in vivo in tumors. We found that ZBP1 expression resulted in tumor cells with a stable polarized phenotype, and reduced their ability to move in response to a gradient in culture. To connect these results on cultured cells to the reduced metastatic ability of these cells, we used multiphoton imaging in vivo to examine tumor cell behavior in primary tumors. We found that ZBP1 expression actually reduced tumor cell motility and chemotaxis, presumably mediating their decreased metastatic potential by reducing their ability to respond to signals necessary for invasion.

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Available from: Kyle Lapidus, May 05, 2014
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    • "It is well established that the translational regulation of localized mRNA has a direct impact on cancer development and metastasis (Rodriguez et al., 2008). For example, the protein levels of the mRNA localization factors ZBP1 and IMP1 directly influence metastasis and tumor progression (Gu et al., 2008, Lapidus et al., 2007, Wang et al., 2004, Kobel et al., 2007, Dimitriadis et al., 2007). LATS/ NDR kinases are implicated in cellular transformation and growth control (Hergovich et al., 2006, Hergovich & Hemmings, 2009). "
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    • "Cite this article as Cold Spring Harb Perspect Biol 2010;2:a003848 the ZBP1 (Z-DNA-binding protein 1 [Wang et al. 2004; Lapidus et al. 2007]), ROCK (Wyckoff et al. 2006), Mena (Pilippar et al. 2008), cofilin (Wang et al. 2006, 2007b), and EGF receptor (Xue et al. 2006; Kedrin et al. 2009) pathways. The results of these studies confirm that the motility pathways are synergistic to create tumor cells that have passed through epithelialmesenchymal transformation and are capable of chemotaxis to EGF and penetration of basement membrane barriers using invadopodia (reviewed in Oser et al. 2009). "
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