Effects of the scaffold proteins liprin-α1, β1 and β2 on invasion by breast cancer cells.

Abstract

The expression of the scaffold protein liprin-α1 is upregulated in human breast cancer. This protein is part of a molecular network that is important for tumour cell invasion in vitro. Liprin-α1 promotes invasion by supporting the protrusive activity at the leading edge of the migrating tumour cell and the degradation of the extracellular matrix by invadopodia. In this study, we have addressed the role of liprin-α1 in the invasive process in vivo and of liprin-proteins in tumor cell motility. The human tumour cell line MDA-MB-231 expresses liprin-α1 and is able to promote the formation of metastasis in mice. Liprin-α proteins may hetero-oligomerize with the members of the subfamily of the liprin-β adaptor proteins. Analysis of the role of liprin-β1 and liprin-β2 has shown that while liprin-β1 contributes positively to tumour cell motility in vitro; liprin-β2 has a negative effect on both cell motility and invasion. Interestingly, we also observed differential effects on the ability of tumour cells to degrade the extracellular matrix, which is required for efficient invasion by tumour cells. In addition, analysis of the formation of lung metastases in vivo revealed that while the overexpression of liprin-α1 in MDA-MB-231 cells did not evidently affect the metastatic process, silencing of the endogenous protein strongly impaired the formation of metastases by two independent invasion assays, without inhibiting the growth of primary tumours. Our data support an important role of distinct liprin family members in the regulation of tumour cell invasion, highlighting pro-invasive and anti-invasive effects by liprin-α1 and liprin-β2, respectively. Our results indicate the importance of liprins in breast cancer cell invasion, and are expected to lead to future investigations on the mechanisms underlying the effects of distinct liprin proteins in different processes linked to tumor cell migration and invasion.