B-cell lymphoma 6 in breast cancer: molecular mechanisms and clinical significance.

Abstract

Breast cancer is the most frequent malignancy and the most common cause of cancer-related death in women worldwide. Despite remarkable improvements in therapy, the prognosis of advanced breast cancer remains poor. Further investigations are mandatory to explore the molecular pathophysiology. Recent studies provide evidence that B-cell lymphoma 6 (BCL6) may play important roles in breast cancer progression. BCL6, a transcriptional suppressor, is critical in the initiation and maintenance of the germinal centers by regulating the formation and function of germinal center B cells, follicular helper T cells and follicular regulatory T cells. It is a well-known key oncogene in lymphomagenesis. In this narrative review, we have summarized the current knowledge of its expression levels in primary breast cancers, analyzed its pathophysiological functions in breast cancer cells, and discussed the underlying molecular mechanisms. The data highlight that elevated BCL6 is significantly related to malignant properties of breast cancer, including tumor size, grade, invasion, metastasis, recurrence, therapy resistance, and poor prognosis. Moreover, elevated BCL6 is tightly associated with cancerous cellular features, such as increased proliferation and survival, poor differentiation, augmented migration, and formation of cancer stem cells, through diverse molecular pathways. In particular, enhanced BCL6 is observed in triple negative breast cancer and linked to decreased progression-free survival of patients. These findings strongly suggest that BCL6 plays a key role in breast cancer development and that targeting BCL6 may be a novel strategy for the treatment of breast cancer.