Biology Reference
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RKIP Suppresses Invasion and
Metastasis
RKIP, as the terminology implies, inhibits Raf-1 kinase activity and regulates the
MAPK signalling pathway (Trakul et al., 2005; Yeung et al., 1999). Besides MAPK
signalling, RKIP function impinges upon GPCR and NK-κB signalling pathway.
Much evidence has accumulated in recent years supporting the view that RKIP sup-
presses invasion and metastasis by regulating EMT, angiogenesis and apoptosis.
RKIP is believed to accentuate apoptosis induced by chemotherapeutic agents and
radiation. Its loss in tumours is said to afford protection against apoptosis (Woods
et al., 2008). Loss or reduced RKIP activity has been linked with chromosomal insta-
bility and abnormalities. RKIP can mechanistically regulate the progression of the
cell cycle by regulating the function of cell cycle checkpoints. RKIP thus coheres
together and influences many aspects of the cancer phenotype.
RKIP Downregulation Creates Chromosomal Instability and
Abnormalities
Chromosomal and cytoskeletal events in mitosis involve the function of mitotic
kinases. Several protein kinases have been implicated in the formation and func-
tion of the mitotic spindle. Notable among them are Aurora kinases which are over-
expressed in human cancers and whose enhanced expression correlates with DNA
and chromosomal aneuploidy. Mitotic kinases have also been implicated in apopto-
sis. Aurora B kinase deletion produces defects in late anaphase and in cell division,
for it seems to be required for sister chromatid separation and segregation. Aurora
B deletion presumably affects microtubule dynamics. Mitotic kinases appear to be
regulated by p53, which monitors the G1-S and the G2-M transition checkpoints
(Sherbet, 2006). There is a large body of evidence that RKIP regulates Aurora B
kinase and the spindle checkpoint of the M-phase via the Raf-1/MEK/ERK cascade.
Loss of RKIP and increased Raf activity allows these cells to circumvent the spin-
dle checkpoint resulting in chromosomal abnormalities (Al-Mulla et al., 2011; Eves
et al., 2006; Rosner, 2007). Consistent with this, RKIP expression inversely corre-
lates with chromosomal instability in colorectal cancer samples, and chromosomal
loss has been correlated with loss of RKIP (Al-Mulla et al., 2008).
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