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Good morning.
Robert Weinberg calling in here
from the Whitehead Institute
for Biomedical Research
in the MIT Department
of Biology,
both in Cambridge,
Massachusetts, USA.
My talk today will be
on the mechanisms of metastasis,
focusing ostensibly
on the genetics of metastasis,
but in fact there will be
great emphasis
on the non-genetic mechanisms
of metastasis, that is,
changes in epigenetics,
the control
of gene transcription
and how that effects
the biology of cancer cells
that are in the course
of metastasizing.
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In the first slide here,
we see a description
of how colorectal carcinogenesis
proceeds as first enunciated,
described
by Kinsler and Vogelstein
in 1989.
And what we see here
is that when one moves
progressively
from a normal colonic
epithelial tissue
towards a primary tumor,
which in this case
is labeled a carcinoma,
one sees
a series of intermediate steps
which involve the accumulation
of distinct genetic alterations
including the loss of APC,
chromosome 18 associated
to tumor suppressor gene,
the loss of P53,
and the activation
of the K-ras oncogene.
And together,
these operate in concert
to create a primary tumor.
The question is, however,
what happens subsequently
when the carcinoma
depicted on the slide
to the right actually begins
to disseminate,
that is send cells
to distant tissues
in the case of colon cancer,
for example, into the liver.
The question of
what goes on here
is critically important
because of the important role
of metastases
in generating a large proportion
of cancer
associated mortality.
