Overexpression of HER2 (human epidermal growth factor receptor 2) is found in about 25 percent of breast cancers and is associated with poor outcomes. HER2-amplified breast cancers use signaling through a complex of proteins called mTORC2 to drive tumor formation, tumor cell survival and resistance to HER2-targeted therapies.
Rebecca Cook, Ph.D., and colleagues have now explored a role for mTORC2 signaling in migration, invasion and metastasis in HER2-amplified breast cancer.
Using genetically modified mouse and cell models and pharmacological inhibitors, the researchers demonstrated that mTORC2 signaling is required for metastasis in HER2-amplified breast cancer. They further showed that the mTORC2 complex signals through two parallel pathways to activate a protein called Rac1, which then drives invasion and motility of breast cancer cells.
The findings, reported June 30 in the journal Breast Cancer Research, add to the increasing evidence that mTORC2 plays key roles in cancer formation, progression, and metastasis.
This research was supported by grants from the National Institutes of Health (CA098131, CA068485, CA195989, TR000445).