Scientists at The University of Texas M. D. Anderson Cancer Center have found that an over-expressed protein can convert active but non-invasive breast cancer into a different cell type, and thereby turn it into invasive breast cancer.
The researchers say that overexpression of the protein 14-3-3? (zeta) launches a molecular cascade that removes bonds that tie the pre-malignant cells together, and hold them in place, converting them from stationary epithelial cells to highly mobile mesenchymal-like cells.
This epithelial-to-mesenchymal transition (EMT) is recognized as a crucial step in metastasis, the spread of cancer to distant organs that causes 90 percent of all cancer deaths.
"We have discovered a key molecular mechanism for the deadly transition of non-invasive breast cancer into invasive disease," said senior author Dr. Dihua Yu.
The researchers have shown that the zeta protein teams up with the oncoprotein ErbB2, also known as HER2, in a two-hit process to convert normal mammary cells to invasive cancer cells.
The findings of the study also provided a biomarker in zeta to identify high-risk patients for more aggressive treatment before their noninvasive breast cancer converts to invasive disease.
The researchers also got new therapeutic targets among the components of the molecular pathway launched by zeta.
According to Yu, some drugs already aim at these targets.
In addition, they found a solution to a puzzling mystery about how a subset of non-invasive breast cancer with excessive presence of an ErbB2/HER2 develops into invasive breast cancer.
Earlier, the researchers showed that zeta is over-expressed in many other cancer types, like lung, liver, uterine, stomach cancers.
"Our findings might have broader implications relating to the mechanism of invasion and metastasis in other types of cancer," Yu said.
The researchers said that it would be very challenging to target zeta by drugs because it also regulates other important proteins in normal cellular processes.
The study has been published in the journal Cancer Cell.