Malic enzyme 2 identified as metabolic target in triple-negative breast cancers with increased serine biosynthesis – UROP Spring Symposium 2023

Malic enzyme 2 identified as metabolic target in triple-negative breast cancers with increased serine biosynthesis

Brisilda Nilaj

Brisilda Nilaj photo

Pronouns: she/her/hers

Research Mentor(s): Mark Slayton
Research Mentor School/College/Department: Internal Medicine, Hematology & Oncology / Medicine
Program: CG
Session: Session 6 (3:40pm – 4:30pm)
Authors: Brisilda Nilaj, Mark Slayton , Jin Heon Jeon, Abhinav Achreja, Zachariah Farah , Yi-Hsien Eu, Alisa Lui, Mason Collard , Liwei Bao , Celina Kleer , Deepak Nagrath, Sofia D. Merajver

Abstract

Cancer is a disease in which mutated cells grow uncontrollably and spread to other parts of the body where they interrupt normal organ function. Every year in the United States, there are about 264,000 cases of breast cancer diagnosed in women and 2,400 in men. Around 42,000 women and 500 men in the United States die each year from breast cancer. Altered metabolism is a major hallmark of cancer; cancerous cells must rewire their metabolism to meet the energetic demands needed for their uncontrolled growth. An important intermediate molecule, pyruvate, is relied upon by multiple metabolic pathways. Pyruvate is produced through many cellular methods, including glycolysis and through the action of malic enzyme 2 (ME2). ME2 converts malate to pyruvate in the mitochondria – in the process, ME2 also converts NADP(+) to NADPH. Here, we explore the reliance of triple-negative breast cancer (TNBC) cell lines on ME2 for optimal growth. We grew TNBC cell lines in regular and serine-free media in cell culture conditions. We used plasmid transfection and lentiviral transduction to modify cells’ genetic content and shut down ME2. With the assistance of the BioTek BioSpa 8 imaging system, we tracked the growth rate of the TNBC lines over multiple days to determine the effect of knocking down ME2. Our experiments distinguish a connection between ME2 and serine metabolism. Knocking down ME2 significantly slowed down the growth in some of the TNBC lines, particularly those with elevated serine biosynthesis. We conclude that ME2 is important for cancerous cell growth and its absence could lead to a therapeutic for the treatment of cancer.

Changing Gears

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