Notch signaling has first been described in murine mammary gland by the proviral integration of mouse mammary tumor virus (MMTV) into the Notch4 locus (Int3 locus) which resulted expression of constitutively active form of Notch4 and transformation of mammary epithelial cells. Notch1 is highly expressed in breast cancer and constitutively active form of Notch1 induces neoplasm. In breast cancer, overexpression of active Notch1 receptor (NICD) promotes epithelial-mesenchymal transition (EMT) via Snail induction which demonstrates the role of Notch signaling in induction of metastasis through EMT. However, the downstream mediators of Notch in EMT, migration and invasion processes are still elusive. In this study, we hypothesized that Notch signaling induces EMT and migration via regulating one or more of the seven candidate genes that are SEMA6D, SEMA3C, CXCR7, CXCL14, CCL20, HMGA2 and CYR61 which were shown to be differentially regulated by Notch signaling in breast cells in microarray data. The candidate genes are involved in EMT and migration in different cell types and tissues. We showed that Notch1 activation in normal breast epithelial cell line MCF10A significantly increased both mRNA and protein expressions of SEMA6D and CYR61 while it significantly reduced SEMA3C and HMGA2 mRNA levels. Notch inhibition led to significant reduction in mRNA expression of CYR61, CCL20 and HMGA2 and protein expression of CYR61 only, while the rest of candidate genes were affected slightly in breast cancer cell line, MDA-MB-231. We chose SEMA6D for further investigation because there is no data indicating the role of SEMA6D in breast cancer in the literature. SEMA6D could be mediator of Notch signaling to induce EMT because it partially rescues negative effect of Notch inhibition on EMT markers. Notch independent effect of SEMA6D suggested that SEMA6D may be involved in inhibiting EMT whereas, it induced migration and cell viability in MDA-MB-231 cell line.Further analysis is required to reveal the role of SEMA6D in EMT and migration.