Inhibiting cell migration in breast cancer

Scientists from the Friedrich Miescher Institute for Biomedical Research (part of the Novartis Research Foundation), with colleagues from the University of Fribourg, have discovered a signaling mechanism that controls mobility and metastasis in breast cancer. In breast cancer, the transcription factor Twist1 has been known to play a role in metastasis of breast tumors. However, the intracellular events regulating Twist1 have been poorly understood. The new research shows 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 activates Twist1, 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 cancer cells were less invasive and formed fewer metastases.