Considering that the sensitivity of proteasome inhibitors is related to proteasome activity [25,26], we investigated the effect of Activin A on proteasome activity and explored the mechanism, and declared that CAFs with high secreted levels of Activin A may reduce the sensitivity of breast cancer cells to ixazomib, which might involve the ERK1/2 signaling pathway-mediated inhibition of proteasome activity. The gene discussed is MAPK3; the disease is breast cancer.