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Scientists
reveal actions of key player in Colorectal
Cancer
Newswise — Colorectal cancer
is one of the most prevalent cancers in the
Western world. The tumor starts off as a
polyp but then turns into an invasive and
violent cancer, which often spreads to the
liver. In an article recently published in
the journal Cancer Research, Prof. Avri Ben-Ze’ev
and Dr. Nancy Gavert of the Weizmann
Institute’s Molecular Cell Biology
Department reveal mechanisms that help this
cancer metastasize.
In a majority of cases,
colorectal cancer is initiated by changes in
a key protein – beta-catenin. One of the
roles of this protein is to enter the cell
nucleus and activate gene expression. But in
colorectal and other cancers, beta-catenin
over-accumulates in the cell and
inappropriately activates genes, leading to
cancer.
Surprisingly, one of
the genes activated by beta-catenin, which
had been previously detected in colorectal
cancer cells by Ben-Ze’ev’s group, codes for
a receptor called L1-CAM. This receptor is a
protein usually found on nerve cells, where
it plays a role in nerve cell recognition
and motility. What is this receptor doing in
cancer cells? Ben-Ze’ev’s previous research
had shown that L1-CAM is only expressed on
certain cells located at the invasive front
of the tumor tissue, hinting that it could
be an important player in metastasis.
In this study, the
scientists found that colorectal cancer
cells engineered to express the L1-CAM gene
indeed spread to the liver, while those
cells lacking L1-CAM did not.
In collaboration with
Prof. Eytan Domany and research student
Michal Sheffer of the Institute’s Physics of
Complex Systems Department, Ben-Ze’ev then
compared the expression of genes induced by
L1-CAM in cultured colon cancer cells to
those in 170 samples of colorectal cancer
tissue removed from patients, and in 40
samples of normal colon tissue. Out of some
160 genes induced by L1-CAM, about 60 were
highly expressed in the cancerous tissue,
but not in normal colon tissue. Ben-Ze’ev
plans to conduct further research into the
role of these genes, to uncover L1-CAM’s
function in metastasis.
Prof. Avri Ben-Ze’ev’s
research is supported by the Jean-Jacques
Brunschwig Fund for the Molecular Genetics
of Cancer; Curie–Weizmann; and the Eugene
and Delores Zemsky Charitable Foundation
Inc. Prof. Ben-Ze’ev is the incumbent of the
Samuel Lunenfeld-Reuben Kunin Chair of
Genetics.
The Weizmann Institute
of Science in Rehovot, Israel, is one of the
world's top-ranking multidisciplinary
research institutions. Noted for its
wide-ranging exploration of the natural and
exact sciences, the Institute is home to
2,600 scientists, students, technicians, and
supporting staff. Institute research efforts
include the search for new ways of fighting
disease and hunger, examining leading
questions in mathematics and computer
science, probing the physics of matter and
the universe, creating novel materials, and
developing new strategies for protecting the
environment.
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