Effect of the Adiponectin Signaling Pathway on Plasma Membrane Order
MetadataShow full item record
Cancer is the second leading cause of death in the world. It is responsible for 16% of death around the world, making it a major health concern in the 21th Century. Approximately, 18.1 million people were diagnosed with cancer in 2018 alone and the numbers are projected to increase even further. Among the major types of cancer, colorectal cancer is the third most prevalent and deadliest cancer type. It is promising to note that up to 75% of colorectal cancer cases could be prevented with dietary modifications, lifestyle changes, and regular screening. Due to the highly preventative nature of the disease, it is critical to understand the mechanisms behind colorectal cancer initiation and proliferation. Adiponectin is an adipose tissue-derived adipokine, whose levels are inversely related to colorectal cancer. With the consensus in the literature that obesity results in low circulating levels of adiponectin, a cancer risk factor, it is pertinent to determine the mechanism by which adiponectin signals through its respective receptors to affect cancer initiation. Recently, our lab showed that AdipoRon, a small-molecule adiponectin receptor agonist, reduces plasma membrane order in a cholesterol-dependent manner. Because cholesterol makes up almost 30% of the total lipids present in the plasma membrane, its structural role and homeostasis is essential for proper signaling through the plasma membrane. Because the plasma membrane serves as a nexus integrating intracellular components that enable various fundamental cellular signaling, including cell proliferations, we hypothesized that AdipoRon signals through AdipoR1 and AdipoR2 to initiate cholesterol mobilization from the plasma membrane, causing a decrease in membrane order. Moreover, we hypothesized that disrupting adiponectin signaling through knocking out AdipoR1 and AdipoR2 would result in an increase in plasma membrane order. Here, we demonstrate that AdipoRon decreases membrane order in a dose-dependent manner in WT HAP1 cells. Moreover, using both confocal imaging and imaging flow cytometry, we show that disrupting adiponectin signaling by knocking out either individual or both adiponectin receptors changes the order of the plasma membrane. These findings are noteworthy because they may in part explain how adiponectin protects against colorectal cancer in part by altering plasma membrane order.
Jung, Kyung Ho (2020). Effect of the Adiponectin Signaling Pathway on Plasma Membrane Order. Undergraduate Research Scholars Program. Available electronically from