Extracellular Hsp90 and TGFß regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model.
BMC Cancer
; 17(1): 202, 2017 03 16.
Article
em En
| MEDLINE
| ID: mdl-28302086
ABSTRACT
BACKGROUND:
Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown.METHODS:
The paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and its lymph node metastasis, respectively, were used as an in vitro model to study key cellular processes required for metastasis. The status of the TGF-ß pathway was examined in these cells using ELISA, flow cytometry, western blot analysis and confocal microscopy. Furthermore, the effect of addition or inhibition of the TGF-ß pathway and Hsp90 on adhesion, migration and anchorage-independent growth, was determined in the cell lines.RESULTS:
When comparing the canonical TGF-ß1 pathway in the genetically paired cell lines our data suggests that this pathway may be constitutively active in the SW620 metastasis-derived cell line and not the SW480 primary tumour-derived line. In addition, we report that, when present in combination, TGF-ß1 and Hsp90ß stimulate anchorage-independent growth, reduce adhesion and stimulate migration. This effect is potentiated by inhibition of the TGF-ß1 receptor and occurs via an alternate TGF-ß1 pathway, mediated by αvß6 integrin. Interestingly, in the SW620 cells, activation of this alternate TGF-ß1 signalling machinery does not appear to require inhibition of the canonical TGF-ß1 receptor, which would allow them to respond more effectively to the pro-metastasis stimulus of a combination of Hsp90ß and TGF-ß1 and this could account for the increased migratory capacity of these cells.CONCLUSIONS:
In this study we report an apparent synergy between TGF-ß1 and Hsp90ß in stimulating migratory behaviour of colon cancer cells when signalling occurs via αvß6 integrin as opposed to the canonical TGF-ß1 pathway.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
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Proteínas de Choque Térmico HSP90
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Proliferação de Células
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article