Discovery of antitumor lectins from rainforest tree root transcriptomes

Abstract

Glycans are multi-branched sugars that are displayed from lipids and proteins. Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival. Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy. Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death. This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence. Remarkably, ML6 displays antitumor activity that is >10 5 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells. This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors. Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydratedirected therapies. Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer. OPEN ACCESS Citation: Lawanprasert A, Guinan CA, Langford EA, Hawkins CE, Sloand JN, Fescemyer HW, et al. (2020) Discovery of antitumor lectins from rainforest tree root transcriptomes. PLoS ONE 15 (2): e0229467. https://doi.org/10.

Bladder Cancer Cells Interaction with Lectin-Coated Surfaces under Static and Flow Conditions

“…The most common approach uses lectins (i.e., plant glycoproteins) to recognize a specific glycan structure attached to various surface receptors [26]. The interest in exploiting glycans' potential in cancer research has increased in recent years [27,28], focusing, for instance, on the direct effect of lectins as drugs that induce cell deaths [29][30][31]. Several attempts have used lectins as the main molecules in biosensor development for cancer cell recognition at the single-cell level [23,32,33].…”

Concanavalin A inhibits human liver cancer cell migration by regulating F‑actin redistribution and assembly via MAPK signaling pathway

“…Plant lectin is a kind of protein molecule derived from natural plants, which has been described as a class of toxic protein that exerts biological effects by binding specifically to glycan ( 6 ). As a toxic protein, plant lectin has been found to have anti-proliferative activity against tumor cells ( 7 , 8 ). In addition, based on the specific sugar-binding ability, plant lectin has also been applied to diagnose malignant and benign tumors with different degrees of glycosylation ( 9 , 10 ).…”