Epithelial-mesenchymal transition (EMT) has recently been associated with
tumor progression,
metastasis, and
chemotherapy resistance in several
tumor types. We performed a differential gene expression analysis comparing
paclitaxel-resistant vs.
paclitaxel-sensitive
breast cancer cells that showed the upregulation of EDIL3 (
EGF Like Repeats and
Discoidin I Like Domains Protein 3). This gene codifies an
extracellular matrix protein that has been identified as a novel regulator of EMT, so we studied its role in
tumor progression and
paclitaxel response. Our results demonstrated that EDIL3 expression levels were increased in
paclitaxel-resistant breast and
prostate cancer cells, and in subsets of high-grade breast and prostate
tumors. Moreover, we observed that EDIL3 modulated the expression of EMT markers and this was impaired by
cilengitide, which blocks the EDIL3-integrin αVβ3 interaction. EDIL3 knockdown reverted EMT and sensitized cells to
paclitaxel. In contrast, EDIL3 overexpression or the culture of cells in the presence of EDIL3-enriched medium induced EMT and
paclitaxel resistance. Adding
cilengitide resensitized these cells to
paclitaxel treatment. In summary, EDIL3 may contribute to EMT and
paclitaxel resistance through autocrine or paracrine signaling in
cancer cells. Blockade of EDIL3-integrin αVβ3 interaction by
cilengitide restores sensitivity to
paclitaxel and reverts EMT in
paclitaxel-resistant
cancer cells. Combinations of
cilengitide and
taxanes could be beneficial in the treatment of subsets of breast and
prostate cancers.