Inhibiting cell migration in breast cancer

March 14, 2012
Inhibiting cell migration in breast cancer

(Medical Xpress) -- Scientists from the Friedrich Miescher Institute for Biomedical Research together with colleagues from the University of Fribourg have discovered a signaling mechanism controlling mobility and metastasis in breast cancer. They have been able to thus reduce invasiveness of the cancer cells. This is promising for the development of therapies against the types of breast cancer that readily form metastasis and for which a therapy has yet to be found.

Advances in the treatment of in the last decades have decreased the in breast cancer markedly. Despite these advances, one tough nut to crack remained: breast cancer that migrates early on into other tissues and forms . For these aggressive tumors a therapy has yet to be found.

Scientists from the Friedrich Miescher Institute for together with colleagues at the University of Fribourg have now discovered a handle on these . The scientists in the groups of Brian A. Hemmings and Prof. Curzio Rüegg have been able to elucidate the signaling events that promote invasive behavior and in breast cancer. What is more, they could significantly impair the metastatic potential of these cells by a blockade of the signaling events.

In the breast cancer field, the transcription factor Twist1 has been known to play a role in motility and invasion in metastatic breast tumors. However the intracellular events regulating Twist1 have been poorly understood. The cancer scientist could now show that Twist1 exerts its devastating role through two signaling molecules: Akt and TGFß2. The hyper-activation of Akt, Twist1 and TGFß2 invariably leads to metastasis. It is a vicious cycle that the scientists discovered: Akt phosphorylates and thus activates Twist, which in turn leads to an increased production of TGFß2. And TGFß2 maintains the hyperactive Akt signaling through the TGFß receptor.

When the scientists depleted or inactivated one of the three molecules the cycle was broken, the were less invasive and formed fewer metastases. "The results are promising; all the more that therapeutic entities inhibiting Akt are already in clinical development", comments Gongdua Xue, Postdoctoral Fellow in the group of Brian A. Hemmings and first author of the study. "In addition, we found that in 90% of the invasive breast tumors we tested Twist1 was continuously active. We believe thus that eventually a big fraction of the patients suffering from aggressive, invasive breast cancers could benefit from our findings."

More information: Xue G, et al. (2012) Akt/PKB-mediated phosphorylation of twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGFß signaling axes. Cancer Discovery, 2:193-195; doi:10.1158/2159-8290

Related Stories

No brakes on breast cancer cells

December 16, 2011

Scientists of the German Cancer Research Center have discovered a tiny RNA molecule, called miR-520, which at once blocks two important pathways in the development of cancer in cells. In estrogen receptor-negative breast ...

New point of attack for breast cancer with poor prognosis

March 5, 2012

(Medical Xpress) -- Scientists from the Friedrich Miescher Institute for Biomedical Research describe how the protein phosphatase SHP2 promotes breast cancer with poor prognosis. As they report in the latest issue of Nature ...

Recommended for you

Study reveals new insight into DNA repair

August 3, 2015

DNA double-strand breaks (DSBs) are the worst possible form of genetic malfunction that can cause cancer and resistance to therapy. New information published this week reveals more about why this occurs and how these breaks ...

Strange circular DNA may offer new way to detect cancers

July 30, 2015

Strange rings of DNA that exist outside chromosomes are distinct to the cell types that mistakenly produced them, researchers have discovered. The finding raises the tantalizing possibility that the rings could be used as ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.