The development of breast cancer resistance to endocrine therapies may result from an increase in cellular plasticity, permitting the emergence of a hormone-independent tumor. ADAM proteins are multidomain transmembrane proteins that have a diverse array of functions in both natural physiology and disease. A number of ADAM proteins have been implicated in the occurrence of breast cancer, including ADAM 9, ADAM12, ADAM15, ADAM17, ADAM22, and ADAM28. ADAM22 expression is driven by the coactivator protein SRC-1 in response to tamoxifen treatment in the resistant setting. ADAM22 is an ER-independent predictor of disease-free survival. LGI1 is a neuropeptide that binds ADAM22 in the nervous system. In addition to being a ligand for ADAM11, ADAM22, and ADAM23, LGI1 may play a role as a tumor suppressor. Furthermore, LGI1 may act to reduce cell migration and may impair proliferation. Therapies based on LGI1 may provide a building block for future therapies in ADAM22-positive breast cancer.
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