Title:

BCL6 promotes ovarian cancer metastasis and chemoresistance

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Abstract

Ovarian cancer is the deadliest gynecologic cancer with a five-year survival rate at about 50%. Ovarian spheroids promote chemoresistance and metastasis; hence, understanding the genes associated with spheroid growth and metastasis is crucial in therapy development. Using the Cancer Genome Atlas and CBioPortal, we found that the transcription modulator BCL6, originally found in B-cell lymphoma, is amplified in about 20% of ovarian cancer patients. Similarly, BCL6 is overexpressed and active in many ovarian cancer cell lines using nuclear extracts analysis and BCL6-responsive reporter. However, little is known about its role in ovarian cancer. To determine if BCL6 affects the viability of spheroids, we transfected ovarian cancer cells with siRNA to BCL6 and found that BCL6 is important for ovarian cancer survival. Because spheroids occur in advanced ovarian cancer, we analyzed the effects of BCL6 in 3D formation using micropatterned plates and discovered that BCL6 is also important for 3D spheroid formation. A major problem in advanced ovarian cancer is metastasis; therefore, we wanted to determine if BCL6 plays a role in this process. We overexpressed or downregulated BCL6 and performed a mesothelial clearance assay to assess the invasion step of metastasis. While overexpressing BCL6 enhanced mesothelial clearance by the spheroids, reducing BCL6 expression reduced mesothelial clearance. This suggested that BCL6 promotes ovarian cancer metastasis. Another reason for ovarian cancer low survival rate is drug resistance. We found that siRNA knockdown of BCL6 decreased ovarian cancer viability when incubated with the chemotherapy drug cisplatin. To assess whether BCL6 modulates the immune response, we developed a co-culture system with macrophages of M1 and M2 phenotypes. Taken together, our data suggests that BCL6 is an important transcriptional modulator in ovarian cancer and that targeting BCL6 in the future may be a useful strategy to treat metastatic ovarian cancer.

Authors

First Name Last Name
Duc Nguyen

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Submission Details

Conference GRC
Event Graduate Research Conference
Department Biochemistry (GRC)
Group Oral Presentation
Added April 17, 2020, 11:57 p.m.
Updated April 17, 2020, 11:57 p.m.
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