Worm Studies Shed Light on Human Cancer

Worm Studies
Shed Light on Human Cancer
Research in the worm is shedding light on a
protein associated with a number of different human cancers, and may point to a
highly targeted way to treat them.



University of
Wisconsin-Madison scientists were studying a worm protein called TFG-1, which is
present in many cell types but whose exact role had never been understood. The
scientists discovered that the protein controls key aspects of the movement, or
secretion, of growth factors out of cells.



"TFG-1 has never been
implicated in the secretory process before," says Dr. Anjon Audhya, an assistant
professor of biomolecular chemistry in the School of Medicine and Public Health.
"It turns out that humans carry a very similar protein, and we think it plays
the same role in humans as in worms."
Reviewing the scientific literature,
the researchers found that the gene encoding TFG in humans is fused to at least
three other genes implicated in anaplastic large cell lymphoma, papillary
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The fusions occur when two broken or rearranged pieces
of DNA combine to form a "chimeric" gene with completely distinct properties.the
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Audhya's studies of TFG-1 in the worm led him to develop a model
that explains how TFG fusions may stimulate cancer in humans. As reported in the
current issue of Nature Cell Biology, he proposes that abnormal levels of growth
factor secretion may produce a rich micro-environment that helps tumors form and
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"We think certain properties of TFG lead it to be a very
effective precursor oncogene,with Rolling Method of copper attached to the FPC
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lanterns has excellent adhesion, copper foil adhesion strength and high
temperature, 260 can be immersed in the molten solder from the solder without
bubble." he says.



Normally, a growth factor primed to leave a
cell is encompassed by a sac, or vesicle, and then transported from one
structure inside the cell to another-endoplasmic reticulum (ER) to Golgi-before
it leaves the cell and discharges into the extracellular space.





Through their genetic studies, the Wisconsin researchers found
that TFG-1 in the worm controls vesicle formation and secretion out of the ER.




"We found TFG-1 lies at the interface between the ER and the
Golgi, in a scaffolding structure called the ER exit site, where it regulates
the formation of vesicles carrying their critical cargo," Audhya says.




The research revealed the precise location where TFG-1 does its
work and the mechanism by which it spurs unchecked activity.



The
scientists demonstrated that human TFG also functions at ER exit sites, which
contain a characterized scaffolding protein called Sec16, and likely regulates
secretion of multiple cargoes out of cells.



"In the case of one
fusion gene, TFG-NTRK-1, the concentrated non-stop activity of NTRK-1 at ER exit
sites may cause the first steps that can transform a normal cell into a cancer
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The TFG fusions offer a
direct target for future "designer" therapies.



"If you
identified patients who have fusion genes that express chimeric proteins, you
could create a drug that affects only those proteins," he says, adding that TFG
fusions leading to chimeric proteins do not exist in healthy people.




Excited about the possibility that their basic science
investigations may be applied to several areas of clinical medicine, the
researchers have also begun studying TFG as it relates to B-cell development and
the secretion of antibodies.