Washington: An Indian-origin scientist
-led team claims to have discovered a culprit in breast cancer
-- a master control switch with the power to set off a cascade
of reactions orchestrated by a cancer-causing gene named Wnt1.
Although the cancer-causing gene (or oncogene) Wnt1
has been connected with breast cancer for over 30 years, the
signals that trigger it remain largely unknown.
Now, Prof Rakesh Kumar of Washington University School
of Medicine and Health Sciences and colleagues have pinpointed
the so-called switch which sparks a type of Wnt signalling in
breast cancer, the `Cancer Research` journal reported.
Moreover, the scientists say that this master
control switch may explain why increased levels of a protein
called MTA1 (metastasis-associated protein 1) are oncogenic in
certain types of breast cancer.
Like many molecular pathways underlying cancer, Wnt
pathways govern normal processes like embryonic development
and the communication between cells in healthy people. For
reasons little understood, however, certain types of Wnt
proteins sometimes go awry, sending off cascades of signals
that turn normal cells into cancerous ones.
In their research, the scientists have implicated MTA1
and a shorter variation of the protein, MTA1s, in Wnt1 (a type
of Wnt) pathway activation. MTA1 belongs to the MTA family of
genes, which help a range of cancers progress in many ways.
The team found that MTA1 expression triggers
cancer-causing signals from Wnt1 in human breast cancer cells.
This Wnt1 signaling cascade leads to tumors, they demonstrate,
by showing that 8.8 percent of mice bearing artificially
elevated levels of MTA1s grew tumors in their mammary glands.
To get down to the details, Kumar and his colleagues
show that MTA1 and MTA1s activate the cancer-causing pathway
by reducing the levels of a protein known as Six3. This
protein is known to inhibit Wnt1 in brain cells, but in their
study involving breast cancer cells, it inhibited Wnt1 in a
rather non-intuitive way.
Six3 normally puts the brakes on Wnt signaling, and so
when MTA1 obstructed Six3, Wnt1 signals let loose.
In addition, the team found that MTA1s also promoted
Wnt signaling directly and through another known Wnt-related
pathway -- namely ERK-mediated GSK3?.
Because inflammation may drive MTA1, and since
inflammation is believed to drive certain forms of cancer,
Kumar`s study suggests one possible reason for why worsening
cancer progression has been correlated with other inflammation
"We`ve raised the next level question, and now we`re
going back into the lab to ask if this pathway plays a role in
inflammation-related cancer," Kumar said.