THBS4 and breast cancer: In other cancer types, such as gallbladder cancer, CAF-secreted thrombospondin 4 binds to integrin α2 on cancer cells, leading to Akt-dependent phosphorylation of heat shock factor 1 and maintenance of the cancer cell’s malignant phenotype (including proliferation, epithelial-to-mesenchymal transition, and stemness).[49] In breast cancer, CAFs secrete collagen to activate the integrin β1/PI3K/Akt pathway, thus regulating microtubule-directed chemoresistance.