Grant: Project Grant

HER2 is overexpressed in about 30% of all breast cancer and is associated with a poor prognosis. We have identified a protein termed SLK that is required for cell growth, motility and invasion. We have genetically deleted this protein in a mouse model of HER2+ breast cancer. Surprisingly, deletion of SLK enhanced tumor growth in a HER2+ model, suggesting that the targeting of one system results in the activation of compensatory mechanisms allowing tumor progression. We have identified the genetic basis for this compensation. We find that SLK deletion leads to the activation of another gene called SOX10, often expressed in triple negative breast cancer. Activation of SOX10 in HER2+ mice leads to the activation of genes associated with more aggressive cancers. We will test the double deletion of SLK and SOX10 on HER2+ breast cancer development and progression. We predict that a double deletion will markedly impair cancer development and could pave the way for the use of combination therapy targeting both SLK and SOX10 to suppress HER2 breast cancer progression.