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, Prof. 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, Prof. Kumar’s study suggests one possible reason for why worsening cancer progression has been correlated with other inflammation -inducers.

“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,” Prof. Kumar said.

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