Targeting Post-Translational Modifications to Improve Combinatorial Therapies in Breast Cancer: The Role of Fucosylation

Abstract

Various tumors rely on post-translational modifications (PTMs) to promote invasiveness and angiogenesis and to reprogram cellular energetics to abate anti-cancer immunity. Among PTMs, fucosylation is a particular type of glycosylation that has been linked to different aspects of immune and hormonal physiological functions as well as hijacked by many types of tumors. Multiple tumors, including breast cancer, have been linked to dismal prognoses and increased metastatic potential due to fucosylation of the glycan core, namely core-fucosylation. Pre-clinical studies have examined the molecular mechanisms regulating core-fucosylation in breast cancer models, its negative prognostic value across multiple disease stages, and the activity of in vivo pharmacological inhibition, instructing combinatorial therapies and translation into clinical practice. Throughout this review, we describe the role of fucosylation in solid tumors, with a particular focus on breast cancer, as well as physiologic conditions on the immune system and hormones, providing a view into its potential as a biomarker for predicating or predicting cancer outcomes, as well as a potential clinical actionability as a biomarker.

Chemical proteomic approach for in-depth glycosylation profiling of plasma carcinoembryonic antigen in cancer patients

“…It was consistent with the fact that increased sialylation contributed to metastasis [29] . Fucosylation has been involved in the tumor recurrence [30] , and core-fucosylation contributed to dismal prognoses and metastatic potential [31] . Fucosylation of CEA from 8 individuals was an impressive feature, which accounted for around 70%.…”

A “One-Step” Strategy for the Global Characterization of Core-Fucosylated Glycoproteome

“…For the "one-step" procedure, probe 1 was added to the solution of 4 for three times every 1 h in the presence of EndoF3-D165A to capture 4. For the "two-step" procedure, probe 2 was added to the solution of 4 for five times every 0.5 h in the presence of EndoF3-D165A to produce an azidopeptide (5). 5 was linked with compound 2 at room temperature for 1 h. Then, the temperature of the above mixtures was raised to 40 °C to precipitate the PNIPAM compounds.…”

“…The formation of core fucosylation is catalyzed by a single enzyme_fucosyltransferase 8 (FUT8) in humans . Emerging evidence indicates that core fucosylation is associated with inflammation and cancer aggressiveness . An aberrant increase in core fucosylation is observed during tumorigenesis in various cancers, such as hepatocellular carcinoma (HCC), non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), etc. − Many studies indicate that increased core fucosylation promotes proliferation, invasion, metastatic potential, and therapy resistance. − The core-fucosylated alpha-fetoprotein (AFP) has been approved by the Food and Drug Administration (FDA) as a clinical HCC diagnostic marker.…”

“… 4 Emerging evidence indicates that core fucosylation is associated with inflammation and cancer aggressiveness. 5 An aberrant increase in core fucosylation is observed during tumorigenesis in various cancers, such as hepatocellular carcinoma (HCC), non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), etc. 6 − 8 Many studies indicate that increased core fucosylation promotes proliferation, invasion, metastatic potential, and therapy resistance.…”

Research progress in cell therapy for oral diseases: focus on cell sources and strategies to optimize cell function

“…The results revealed no clear signs of cell proliferation after the transplantation of green fluorescent protein (GFP)-BMSCs, but the adequate stromal generation and clearance capacity of BMSCs could repair the cartilage of the osteoarticular processes. Furthermore, the repair effect was reversed when BMSCs were stopped from being delivered to arthritic joints ( Antonarelli et al, 2023 ).…”