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2014 ; 171
(24
): 5507-23
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Movers and shakers: cell cytoskeleton in cancer metastasis
#MMPMID24665826
Fife CM
; McCarroll JA
; Kavallaris M
Br J Pharmacol
2014[Dec]; 171
(24
): 5507-23
PMID24665826
show ga
Metastasis is responsible for the greatest number of cancer deaths. Metastatic
disease, or the movement of cancer cells from one site to another, is a complex
process requiring dramatic remodelling of the cell cytoskeleton. The various
components of the cytoskeleton, actin (microfilaments), microtubules (MTs) and
intermediate filaments, are highly integrated and their functions are well
orchestrated in normal cells. In contrast, mutations and abnormal expression of
cytoskeletal and cytoskeletal-associated proteins play an important role in the
ability of cancer cells to resist chemotherapy and metastasize. Studies on the
role of actin and its interacting partners have highlighted key signalling
pathways, such as the Rho GTPases, and downstream effector proteins that, through
the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An
emerging role for MTs in tumour cell metastasis is being unravelled and there is
increasing interest in the crosstalk between key MT interacting proteins and the
actin cytoskeleton, which may provide novel treatment avenues for metastatic
disease. Improved understanding of how the cytoskeleton and its interacting
partners influence tumour cell migration and metastasis has led to the
development of novel therapeutics against aggressive and metastatic disease.
LINKED ARTICLES: This article is part of a themed section on Cytoskeleton,
Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view
the other articles in this section visit
http://dx.doi.org/10.1111/bph.2014.171.issue-24.