Isoform Specific Function of the Metastatic Formin FMNL2

Abstract

Cancer cell metastasis is induced by actin-dependent cell migration and is affected by cytoskeletal remodelling proteins. FMNL2 is one such protein which promotes colorectal cancer (CRC) cell metastasis and amoeboid style invasion of melanoma cells. FMNL2 mRNA is subject to alternative splicing and studies suggest that the resulting encoded proteins are likely to differ in their regulation, subcellular localization and activity. We identified four FMNL2 isoforms (ITM, YHY, PMR and TQS) expressed in non-invasive (SW480) and invasive (SW620) CRC cells, as well as in highly invasive A375 amoeboid melanoma cells. qPCR data suggests that an “invasive” isoform (TQS) may be preferentially expressed in highly invasive and amoeboid cell lines. Boyden chamber invasion assay results show that FMNL2 knockdown inhibits amoeboid style invasion in two melanoma cell lines and that TQS is the most efficient isoform at rescuing the invasive phenotype. This study provides a further understanding of FMNL2’s role in invasion and metastasis and identifies specific targets for the development of future antimetastatic therapies.