How 'Twist' fuels breast cancers

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Washington, Dec 5 (ANI): A research team led by Indian-origin researcher from John Hopkins University has identified a protein produced by a gene called 'Twist', that when present, drives aggressive, metastatic breast cancer from other breast cancer cells.

In the experiments, Hopkins team focused on the gene "Twist" (or TWIST1) - named for its winding shape - because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes.

Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.

"Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer," said Dr Venu Raman, associate professor of radiology and oncology, Johns Hopkins University School of Medicine.

"The protein it makes is one of a growing collection of markers that, when present, flag a tumour cell as a breast cancer stem cell," Raman added.

Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells

The study has shown that the presence of Twist, along with changes in two other biomarkers - CD 24 and CD44 - even without EMT, announces the presence of this critical sub-group of stem cells.

During the study, researchers worked with human breast cancer cells transplanted into mice, all of which had the oncogene Twist.

They tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells.

They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumours.

Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.

Raman suggests that Twist is integral to the breast cancer stem cell phenotype and has fundamental implications for early detection, treatment and prevention.

The study is published in journal Neoplasia (ANI)

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