Type I collagen down-regulates E-cadherin expression by increasing PI3KCA in cancer cells.

The extracellular matrix (ECM) has been shown to induce the epithelial-mesenchymal transition (EMT), which is characterized by the loss of E-cadherin. However, little is known about the mechanisms by which collagen I, the most abundant component of ECM, induces this process. Here, we show that E-cadherin was down-regulated in response to collagen I in SKOV3 ovarian cancer cells and PC3 prostate cancer cells. Furthermore, collagen I induced the up-regulation of PIK3CA, which in turn contributed to the collagen I-induced down-regulation of E-cadherin by up-regulating its transcriptional repressors, Snail and Slug. Our data demonstrate that PIK3CA is a mediator of collagen I-induced down-regulation of E-cadherin.