The actin cytoskeleton and the nuclear translocation of β-catenin in human oesophageal squamous carcinoma cell lines

[摘要] In addition to its crucial role in cell adhesion, β-catenin is also known to augmentgene expression by forming a complex with lymphoid enhancer factor/T-cellfactor in the nucleus. Unregulated β-catenin expression and/or its increasednuclear presence can lead to abnormal cell proliferation, tumour invasion andmetastasis. Pertinent is the fact that the actin cytoskeleton is central to thetranslocation of several nuclear proteins. This study investigated whether the actincytoskeleton influences the nuclear translocation of β-catenin in humanoesophageal squamous cell carcinoma (HOSCC), a metastatic disease of commonoccurrence in South Africa. Disruption of the actin cytoskeleton of fivemoderately differentiated HOSCC cell lines, with cytochalasin D (cytoD), showedthat the nuclear β-catenin level was unaltered in SNO, WHCO1 and WHCO5, butdecreased in WHCO3 and WHCO6. CytoD treatment did not affect thecytoplasmic/membrane β-catenin level in these cell lines. Further examination ofthe possible association between the actin cytoskeleton and nuclear β-catenintranslocation, required the design and stable transfection, of a vector containingfull-length human β-catenin cDNA into one of the HOSCC lines. Stimulation ofexogenous β-catenin expression in transfected WHCO1 cells did not increasecellular β-catenin level, nor did the stimulation of endogenous β-cateninexpression with DMSO. In most cases (SNO, WHCO1 and WHCO5) the nucleardistribution of β-catenin in HOSCC is independent of a functional actincytoskeleton, nonetheless there are some exceptions (WHCO3 and WHCO6). Theobserved variation within the HOSCC lines is possibly due to specific underlyingevent/s particular to the cell line. The stable level of β-catenin expression could bea consequence of regulatory pathways in WHCO1 compensating for the inducedimbalance of β-catenin expression.

[发布机构] University of the Witwatersrand