Transcription Factor Oct4 Control EMT-relevant Tumor Migration And Invasion Through Regulating SOCE In Breast Cancer Cell

Recently, many researchers have proven that transcription factor Oct4 is related with tumor proliferation and anti-apoptosis in many kinds of cancer cells. However, the role of Oct4 in tumor metastasis and its relevant mechanisms are still undefined. Through comparing the expression of Oct4 in MCF-7 and MDA-MB-231 breast cancer cell lines, which have different invasion and metastasis capability but with the same origin, we discover that Oct4 expresses highly in MCF-7 breast tumor cell line but without significant expression in MDA-MB-231 cell line. Owing to the distinctly different expression of Oct4 in these two cell lines, we try to explore the function of Oct4 in breast cancer migration and invasion. From the results of Transwell assay, we found that silencing Oct4 in MCF-7 cells could highly improve its migration and invasion capability. The Epithelial-mesenchymal transition (EMT) is an important cellular program during tumor migration, invasion and metastasis. Based on these knowledge, we have tested E-cadherin(a marker of epithelial cells) and a-smooth muscle actin expression(a marker of mesenchymal cells) both on protein and mRNA level with western blot and reverse-transcriptase PCR. The results demonstrate that silencing Oct4 factor greatly improved the Epithelial-mesenchymal transition in MCF-7 cell line. It is noteworthy that transcription factor Oct4 is inhibited by TGF-β1 both in dose-dependent and time-course manner.Further, we have demonstrated that silencing Oct4 factor in MCF-7 cell line, STIM1 and Orail (CRAC channel components) are up-regulated, and Ca+ influx directed by CRAC (a kind of store-operated calcium channels) is enhanced. In addition, blocking Ca2+ influx with 2-APB (which is an inhibitor of store-operated calcium channel) or silencing STIM1 in MCF-7 cell line could rescue the epithelial-mesenchymal transition caused by Oct4 silence. In sum, our studies not only show that Oct4 plays a dominant role in breast cancer cell migration and invasion, but also demonstrates that Oct4 improve the epithelial-mesenchymal transition of breast cancer cell by regulating store-operated calcium entry (SOCE) effect.In conclusion, our results not only point out that transcription factor Oct4 probably participates in regulating the EMT process during breast cancer invasion and metastasis, but also elucidate that its function in EMT is owing to the enhanced Ca2+ influx directed by store-operated calcium influx which is regulated by Oct4.