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Role of CXCR4/SDF-1 Alpha in the Migratory Phenotype of Hepatoma Cells That Have Undergone Epithelial-Mesenchymal Transition in Response to the Transforming Growth Factor-Beta

Role of CXCR4/SDF-1 Alpha in the Migratory Phenotype of Hepatoma Cells That Have Undergone Epithelial-Mesenchymal Transition in Response to the Transforming Growth Factor-Beta

Esther Bertran, Laia Caja, Estanis Navarro, Patricia Sancho, Jèssica Mainez, Miguel M Murillo, Antonia Vinyals, Angels Fabra, Isabel Fabregat

Cell Signal. 2009 Nov;21(11):1595-606.

PMID: 19586611

Abstract:

Treatment of FaO rat hepatoma cells with TGF-beta selects cells that survive to its apoptotic effect and undergo epithelial-mesenchymal transitions (EMT). We have established a cell line (T beta T-FaO, from TGF-beta-treated FaO) that shows a mesenchymal, de-differentiated, phenotype in the presence of TGF-beta and is refractory to its suppressor effects. In the absence of this cytokine, cells revert to an epithelial phenotype in 3-4 weeks and recover the response to TGF-beta. T beta T-FaO show higher capacity to migrate than that observed in the parental FaO cells. We found that FaO cells express low levels of CXCR4 and do not respond to SDF-1 alpha. However, TGF-beta up-regulates CXCR4, through a NF kappaB-dependent mechanism, and T beta T-FaO cells show elevated levels of CXCR4, which is located in the presumptive migration front. A specific CXCR4 antagonist (AMD3100) attenuates the migratory capacity of T beta T-FaO cells on collagen gels. Extracellular SDF-1 alpha activates the ERKs pathway in T beta T-FaO, but not in FaO cells, increasing cell scattering and protecting cells from apoptosis induced by serum deprivation. Targeted knock-down of CXCR4 with specific siRNA blocks the T beta T-FaO response to SDF-1 alpha. Thus, the SDF-1/CXCR4 axis might play an important role in mediating cell migration and survival after a TGF-beta-induced EMT in hepatoma cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413120	SDF-1 beta from rat			Price

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