Science - Translational Medicine: Novel Biomarkers for Triple Negative Breast Cancer

Researchers at the Johns Hopkins University School of Medicine have focused on triple-negative breast cancer (TNBC) to uncover key molecular differences between primary and metastatic cancer cel.

"We have long needed new therapeutic targets and options for triple-negative breast cancer," said co-corresponding author Andrew Ewald, PhD, chair of the Department of Cell Biology at the Johns Hopkins University School of Medici.

It is estimated that about 280,000 people are diagnosed with breast cancer in the United States each year, of which about 10%-20% are triple-negative breast cancer patients, and this proportion is higher in African American women, who are more likely to develop the disea.

Triple-negative breast cancer is characterized by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptors on its cell surfa.

For the study, the research team started with three samples, including a mouse model, human cancer implanted in mice, and primary and metastatic disease in eight patients treated at Johns Hopkins Hospit.

"The bad news is that cells from the metastatic site are super-optimized for cell migration and resistance to therapy," .

Specifically, .

To do this, breast cancer cells acquire a cytoskeletal protein called vimentin, which enhances the migration of mesenchymal cel.

At the same time, triple-negative breast cancer cells also gain a survival advantage by producing a protein called E-cadherin, a calcium-dependent cell adhesion molecule normally present in the epitheli.

When triple-negative breast cancer cells acquired this survival and migration property, the scientists classified their cell state as promiscuous epithelial-mesenchymal (EMT) cel.

Using single-cell sequencing analysis, they found that most metastatic cells became a more mobile, more viable promiscuous EMT sta.

At the molecular level, they found that five transcription factors (Grhl2, Foxc2, Zeb1, Zeb2, and Ovol1) are required for cancer cell invasion and colony formati.

The team he leads is studying how to block the genes of transcription factors or the proteins they produce to stop the growth of metastatic cance.

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