Biology Reference
In-Depth Information
Ras
Ral/GDS
ERK 1/2 pathway
Pathway
Cell proliferation
Cytoskeletal organisation
Invasion
Raf1/
MEK/ERK/ELK
PI3K pathway
Cell proliferation
Development
Rac/GDF-GTP
PIP2
PIP3
Akt
mTOR
Rac1
Bad/Bcl-XL
Caspase
NF-
B
cascade
Apoptosis
Figure 28.1
The three major pathways of Ras signalling, with particular focus on Akt
signalling affecting apoptosis and cell population size. Akt inhibits FasL-mediated apoptosis.
This is not shown here. The ERK and Ral/GDS (guanine nucleotide dissociation stimulator)
pathways transduce Ras signal to promote cell proliferation, modulate cytoskeletal
organisation and induce cell motility and invasion. Signalling along these two pathways can
synergise in their phenotypic effect and lead to the generation of an aggressive phenotype.
expression in human tumours correlated with reduced levels of p21 together with
loss of growth arrest (Morton et al., 2010). Overall these findings are underwhelm-
ing and unremarkable
per se
. The association of EGFR on LKB1 is rather tenuous
but deserves investigation in other tumours, as also the putative links with Ras and
p53. One would do well to recall there that EGFR expression might be co-ordinately
regulated by suppressor genes such as nm23, and conversely nm23 can negatively
regulate EGF/EGFR and Ras-mediated activation of the ERK pathway and cellular
proliferation.
LKB1 in Cross Talk with Oestrogens and ER/HER2
Aside from its conventional roles of regulating the cell cycle and cell proliferation
and apoptosis, p53 seems to be associated with the regulation of lipid metabolism
(Goldstein and Rotter, 2012). With the pervasive infiltration of conventional signal-
ling systems operating growth signal transduction into the LKB1 suppressor function
and given that LKB1 also regulate glucose and lipid metabolism and further that p53
is a target of ERα, it would be appropriate to look at ER/HER2 in the backdrop of
the LKB1 scenario, with its inherent contradictions and varied nuances.
ERα as a tumour promoter has marked influence on the expression of other
suppressor genes. It downregulates NDRG1 and their expressions are inversely
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