SPP1 and breast cancer: Of note, osteopontin, a bone matrix protein, has been shown to noncanonically activate GLI1 in breast cancer to promote the acquisition of mesenchymal phenotype via upregulation of mesenchymal (N-cadherin, vimentin, TWIST, and SLUG) and downregulation of epithelial (E-cadherin and keratin-18) markers, as well as promote drug resistance to doxorubicin, paclitaxel, and cisplatin via upregulation of ABC transporters (ABCB1 and ABCG2).