My research focuses on investigating the role of core-fucosylation in breast cancer metastasis. Core-fucosylation, the attachment of an α1,6-fucose to the innermost N-acetylglucosamine (GlcNAc) of N-glycans by fucosyltransferase 8 (FUT8), is a common protein glycosylation modification implicated in cancer. Elevated FUT8 expression and increased core-fucosylation are hallmark features in various cancers, including lung and breast cancer. Previous studies have demonstrated that FUT8 is significantly overexpressed in breast tumors compared to normal tissues and that genetic knockdown or pharmacological inhibition of FUT8 markedly reduces tumor metastasis.
In addition, core-fucosylation plays a critical role in cancer immunology, particularly in the paracrine signaling interactions between tumor cells and macrophages that drive metastatic progression. Macrophages in the tumor microenvironment (TME) are broadly categorized into M1 and M2 functional phenotypes. M1 macrophages are classically activated and associated with pro-inflammatory responses that help eliminate cancer cells, while M2 macrophages are alternatively activated, promote anti-inflammatory processes, and support tumor metastasis. In most tumors, infiltrating macrophages are predominantly of the M2 phenotype. Macrophages are among the most abundant immune cells in the breast cancer TME and are key players in promoting breast cancer metastasis. However, the role of core-fucosylation in driving tumor-associated macrophage (TAM) M2 polarization remains poorly understood.
My current research aims to determine whether core-fucosylation influences TAM M2 polarization. I have generated a Fut8 knockdown RAW264.7 macrophage cell line using Fut8 shRNA transduction. These cells exhibit severe defects in interleukin-4 (IL-4)-induced M2 polarization, suggesting that core-fucosylation is critical for this process.
In the future, I plan to investigate the molecular mechanisms by which core-fucosylation influences TME polarization and explore how targeting Fut8 in TAMs affects the tumor microenvironment and tumor metastasis.
Post-doctoral Fellowship - Indiana University School of Medicine, Indianapolis, IN 2015-2018
Ph.D. - East Carolina University, Greenville, NC 2010-2014