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Isoform Specific Function of the Metastatic Formin FMNL2

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.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OOU.#10393/24396
Date13 August 2013
CreatorsPéladeau, Christine
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeThèse / Thesis

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