Presentation Title

Examining the Role of Scaffold Attachment Factor B1 in Triple Negative Breast Cancer Metabolism

Faculty Mentor

Benny A. Kaipparettu

Start Date

23-11-2019 9:00 AM

End Date

23-11-2019 9:15 AM

Location

Markstein 210

Session

oral 1

Type of Presentation

Oral Talk

Subject Area

biological_agricultural_sciences

Abstract

Cancer cells are thought to produce ATP energy by having a high rate of glycolysis and high quantities of lactate, known as the Warburg effect. However, recent experimental data suggests that cancer cells also rely on mitochondrial-oxidative phosphorylation through alternative energy pathways like fatty acid beta-oxidation (FAO). Triple Negative Breast Cancer (TNBC) is one of the most aggressive and highly metastatic types of breast cancer, with no therapeutic options currently available for reducing its severity. Scaffold Attachment Factor B1 (SAFB1) is a matrix binding protein that acts as an anchor on eukaryotic DNA allowing for the organization of genetic information in the nucleus. SAFB1 is a possible tumor-suppressor and has been shown to act as an estrogen-receptor (ER) corepressor in ‘ER-positive’ breast cancer, along with participating in cell cycle regulation and cellular stress-response. I focused on how SAFB1 might influence tumor progression and metabolism in FAO-dependent TNBC. I modulated the SAFB1 level in TNBC cells examining specific genes that are known to regulate glycolysis and FAO pathways. I utilized methods such as quantitative polymerase chain reaction (qPCR), western blot, and cell viability (thiazolyl-blue tetrazolium-blue; MTT) to determine how various SAFB1 knockdowns affect these metabolic processes in MDA-MB-231 and SUM159 TNBC cell lines. From qPCR and western blot analysis, I observed that a SAFB1 knockdown in TNBC cells induces the expression of the FAO rate-limiting enzyme CPT1 while decreasing the expression of glycolysis associated genes LDHA and Glut1. FAO activates the cSrc pathway by phosphorylating Src at Y419 (pSrc). My experiments suggest that SAFB1 knockdown upregulates pSrc in TNBC cells, signifying that SAFB1 may act as a tumor-suppressor in TNBC tumorigenesis. This data supports the hypothesis that SAFB1-mediated mitochondrial metabolic reprogramming to FAO is important in TNBC tumorigenesis, leading to identifying a novel target for TNBC therapy in the near future.

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Nov 23rd, 9:00 AM Nov 23rd, 9:15 AM

Examining the Role of Scaffold Attachment Factor B1 in Triple Negative Breast Cancer Metabolism

Markstein 210

Cancer cells are thought to produce ATP energy by having a high rate of glycolysis and high quantities of lactate, known as the Warburg effect. However, recent experimental data suggests that cancer cells also rely on mitochondrial-oxidative phosphorylation through alternative energy pathways like fatty acid beta-oxidation (FAO). Triple Negative Breast Cancer (TNBC) is one of the most aggressive and highly metastatic types of breast cancer, with no therapeutic options currently available for reducing its severity. Scaffold Attachment Factor B1 (SAFB1) is a matrix binding protein that acts as an anchor on eukaryotic DNA allowing for the organization of genetic information in the nucleus. SAFB1 is a possible tumor-suppressor and has been shown to act as an estrogen-receptor (ER) corepressor in ‘ER-positive’ breast cancer, along with participating in cell cycle regulation and cellular stress-response. I focused on how SAFB1 might influence tumor progression and metabolism in FAO-dependent TNBC. I modulated the SAFB1 level in TNBC cells examining specific genes that are known to regulate glycolysis and FAO pathways. I utilized methods such as quantitative polymerase chain reaction (qPCR), western blot, and cell viability (thiazolyl-blue tetrazolium-blue; MTT) to determine how various SAFB1 knockdowns affect these metabolic processes in MDA-MB-231 and SUM159 TNBC cell lines. From qPCR and western blot analysis, I observed that a SAFB1 knockdown in TNBC cells induces the expression of the FAO rate-limiting enzyme CPT1 while decreasing the expression of glycolysis associated genes LDHA and Glut1. FAO activates the cSrc pathway by phosphorylating Src at Y419 (pSrc). My experiments suggest that SAFB1 knockdown upregulates pSrc in TNBC cells, signifying that SAFB1 may act as a tumor-suppressor in TNBC tumorigenesis. This data supports the hypothesis that SAFB1-mediated mitochondrial metabolic reprogramming to FAO is important in TNBC tumorigenesis, leading to identifying a novel target for TNBC therapy in the near future.