Artigo Acesso aberto Revisado por pares

CREB3L1 Is a Metastasis Suppressor That Represses Expression of Genes Regulating Metastasis, Invasion, and Angiogenesis

2013; Taylor & Francis; Volume: 33; Issue: 24 Linguagem: Inglês

10.1128/mcb.00959-13

ISSN

1098-5549

Autores

Paul Mellor, Leah Deibert, Brian Calvert, Keith Bonham, Svein A. Carlsen, Deborah H. Anderson,

Tópico(s)

Heat shock proteins research

Resumo

The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cyclic AMP [cAMP]-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low-metastasis or nonmetastatic cell lines. When metastatic cells were transfected with CREB3L1, they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under nonadherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, not only did CREB3L1-expressing cells fail to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and chromatin immunoprecipitation with microarray technology (ChIP on Chip) analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorigenesis and that loss of expression is required for the development of a metastatic phenotype.

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