A new route to curb breast cancer metastases

In the words of Albert Einstein: “Persistence is the most powerful force on Earth, it can move mountains." After a quarter of a century spent studying the CdGAP protein, Nathalie Lamarche-Vane and her team have identified its role in the progression of HER2-positive breast cancer, a type of very aggressive tumor that develops early metastases. The senior scientist at the Research Institute of McGill University Health Center (RI-MUHC) is hopeful that this discovery will lead to new oncological treatments. “We can imagine drugs which would partially inhibit the expression of CdGAP or which would target a specific function of the protein, or neutralize its association with certain partner receptors,” says Lemarche-Vane. By doing so, “we could possibly block the development of the primary tumor and prevent it from producing metastases.” Read: Alarming trend: More young people are getting cancer—and dying of it, study finds Before getting there, she says additional research is necessary to better understand, at the molecular level, the mechanisms induced by CdGAP. “You can't completely inhibit it as there would be too many side effects as it controls several crucial cellular functions,” says Lamarche-Vane, who discovered this protein at the end of the 1990s and remembers having “sequenced” the gene that causes it. Since then, the scientist has established that CdGAP controls the cytoskeleton of cells. It is involved in the regulatory mechanisms of cell proliferation, migration and adhesion. In other words, “it plays a major role in cell division and it serves to make cells move,” she says. In the context of HER2-positive breast cancer, “very high levels of CdGAP expression were observed in cancer cells. By completely inhibiting its expression, we found its role." Read: Looking after survivors Initially, the protein has an effect on the development of primary tumors. “If we remove it, we reduce the growth of the tumor by limiting the proliferation of cancer cells.” The team's research, which was published in the journal Cell Reports, also shows that CdGAP is a molecular target of the TGF-β signaling pathway which positively regulates a gene signature of epithelial-mesenchymal transition (EMT) in HER2-positive cancer cells. This transition generates cells endowed with cellular mobility and invasion capacities which are at the origin of the progression of aggressive cancer metastases. “The TGF-β signaling pathway is required for CdGAP to function. By targeting the association between TGF-β and CdGAP in order to inhibit it, we could stem the metastatic process,” says Lamarche-Vane, noting that it is easier to develop drugs that target receptors externally rather than seeking to directly reach CdGAP which is located inside the cells. This is an avenue that the researcher intends to explore in continuing to dissect this protein. “Fundamental research has priority in the development of new treatments,” she says, This article was translated from French and originally ran in our sister publication Profession Santé.

A new route to curb breast cancer metastases

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