BCL2A1 plays a biphasic role in ovarian cancer progression

Abstract

The high mortality rate of ovarian cancer (OVCA) is due to that most patients are found in advanced stages accompanied with extensive metastasis. Recent evidence has suggested that the intrinsic modification allows metastatic OVCA cells to adapt to the tumor microenvironment during metastatic progression. In this study, we identified a BCL2 family member, BCL2A1, is significantly upregulated in OVCA cells as compared with immortalized normal ovarian surface epithelial cells (HOSE). Intriguingly, BCL2A1 could be induced quickly by different physiological stresses, followed by a gradual reduction. Functionally, enforced expression of BCL2A1 increased foci formation ability in serum starvation medium, anchorage-independent cell growth, and anoikis resistance, indicating BCL2A1 is required for OVCA cell survival in stressed conditions. However, prolonged BCL2A1 expression retarded OVCA cell proliferation in normal culture medium. Conversely, BCL2A1 knockdown restored the cell proliferation rate, while the cell viability of OVCA was abrogated in stress culture condition. Additionally, BCL2A1 knockdown impaired cell migration/invasion ability and anoikis resistance through inhibition of mesenchymal cell marker N-cadherin and Slug expression. These results suggest that BCL2A1 has a biphasic role in governing OVCA cell survival and cell growth in tumor microenvironment during metastatic progression.