Effect of FAK Activation HER2+Breast Cancer

Hormone responsive breast cancer, a type of cancer that grows more aggressively in the presence of certain types of hormones (i.e. estrogen), makes up about 20–30% of all human breast cancers. Trastuzumab (Herceptin) is a common drug treatment that targets the HER receptor and inhibits estrogen from binding. The goal of my research is to understand whether the use of Herceptin to neutralize the HER receptor can be bypassed by the cell by using the cMET pathway. Studies show that drug resistance to Herceptin in HER+ cancers may be the product of the cell using this alternative pathway resulting in FAK activation. FAK activation via the HER and cMET associated signaling pathways is one of the mechanisms for the spread of cancer cells via metastasis. We examined FAK activation and cell movement capacity using MCF‐7 HER2 positive breast cancer cells. Our results show that MCF‐7 breast cancer cells treated with Herceptin still show activation of FAK. Using a migration assay, we see that Herceptin does not inhibit the migration pathway. Treatment significantly (p = 0.01) increased the migration of the MCF7 cells compared to the untreated cells. The cMET specific inhibitor, Tepotinib, significantly reduced migration, indicating that cMET is being used as an alternative pathway to activate migration. Immunoblotting showed that there was no difference in total phosphorylated FAK between the treated and untreated cells, but the ratio of phosphorylated to unphosphorylated FAK is being investigated. These preliminary results suggest that there is the possibility of an alternative pathway that is being used to activate FAK despite the inhibition of the HER receptor. Support or Funding Information Fort Lewis College Student Research, Scholarly and Creativity Grant This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .