A1 Journal article – refereed

FMNL2/FMNL3 formins are linked with oncogenic pathways and predict melanoma outcome

List of Authors: Maria Gardberg, Vanina D Heuser, Ilkka Koskivuo, Mari Koivisto, Olli Carpén

Publication year: 2016

Journal: Journal of Pathology: Clinical Research

Volume number: 2

Issue number: 1

Number of pages: 12

ISSN: 2056-4538

DOI: http://dx.doi.org/10.1002/cjp2.34


While most early (stage I-II) melanomas are cured by surgery, recurrence
is not uncommon. Prognostication by current clinicopathological
parameters does not provide sufficient means for identifying patients
who are at risk of developing metastases and in need of adjuvant
therapy. Actin-regulating formins may account for invasive properties of
cancer cells, including melanoma. Here, we studied formin-like protein 2
and 3 (FMNL2 and FMNL3) in melanoma by analysing their role in the
invasive properties of melanoma cells and by evaluating whether FMNL2
expression is associated with melanoma outcome. Immunohistochemical
characterization of FMNL2 in a cohort of 175 primary cutaneous stage
I-II melanomas indicated that high FMNL2 reactivity correlates with poor
outcome as evaluated by recurrence free survival (p < 0.0001) or
disease specific survival (p < 0.0001). In multivariate analysis,
Breslow's thickness (p < 0.05) and FMNL2 expression (p < 0.001)
remained as independent prognostic factors. Cellular studies revealed
that FMNL2 is a component of filopodia in many melanoma cell lines.
Inhibition of either FMNL2 or the closely related FMNL3 affected the
maintenance of melanoma cell morphology and reduced migration. Finally,
inhibition of the BRAF, PI3K and MAPK oncogenic pathways markedly
reduced expression of both FMNL2 and FMNL3 in melanoma cells. The
results suggest a major role for FMNL2/FMNL3 formins in melanoma biology
and raise the possibility that the novel targeted melanoma drugs may
interfere with the cellular properties regulated by these formins.

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