Moreover, thrombospondin 4 (TSP-4) secreted from CAFs binds to integrin α2 to promote HSF1 phosphorylation at Ser326 to support the malignant phenotypes of gallbladder cancer cells, including cell proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness [84]. This evidence concerns the gene THBS4 and gallbladder cancer.