Kayla Hickman
Research Mentor: Yatrik Shah
Mentor Department: Molecular & Integrative Physiology, Medicine
Author(s): Drew Stark, Kayla Hickman, Brandon Chen, Yatrik Shah
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 17
Abstract
Cancer is a disease of uncontrolled cell growth, requiring tumor cells to rewire their metabolism for survival. Stearoyl-CoA Desaturase (SCD) is an enzyme that generates mono-unsaturated fatty acids (MUFAs) from saturated fatty acids and is highly upregulated in many types of cancers. SCD activity is necessary to maintain lipid levels for membrane generation and as an energy source in cancers. However, SCD has largely failed as a clinical target for cancers of various tissues. Another important feature of lipid saturation is its effect on organelle membrane fluidity, which must be balanced to orchestrate contact sites between organelles. Endoplasmic reticulum-mitochondria contact sites (ERMCS) are a well studied type of contact site important for cellular homeostasis by regulating lipid transport and calcium signaling, and have been linked to diseases like Alzheimer’s, Type 2 Diabetes, and cancer, but how cancer cells regulate ERMCS to rewire metabolism and sustain growth is still unknown. Using a fluorescent reporter of ERMCS, we observe SCD inhibition via small molecule CAY10566 blunts ERMCS induction. However, the mechanism by which SCD inhibition and lipid metabolism mediate ERMCS formation is unknown. We will first confirm the specificity of CAY10566 by genetic knockdown of SCD through small interfering RNAs. We hypothesize that SCD generated MUFAs balance the fluidity between the endoplasmic reticulum and mitochondria membranes, and this fluidity impacts the ability of protein tethers to connect the two organelles for communication and metabolite transportation. Future work will investigate this mechanism to define the role of SCD in ERMCs and cancer cell metabolism.
