Realizing the promise of ‘La Dolce Vita’ via chemical biology: glycan‐motif editing of sLeX for precision cancer therapeutics DOI Creative Commons
Barbara Richichi, Robert Sackstein

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

The convergence of glycochemistry and glycobiology is enabling the creation new therapeutic approaches with unprecedented capacity to alter cell organismic biology using strategies that can uniquely specifically custom-modify expression key surface glycan motifs. We define this evolving field chemical as 'glycan-motif editing', one principal targets glycoengineering effort sialofucosylated terminal lactosaminyl known sLeX (CD15s). This tetrasaccharide structure plays pivotal roles in both steady-state malignant hematopoiesis, regulation immune response, cancer metastasis. Within biological framework, we discuss immense potential glycan-motif editing precision therapeutics will profoundly improve outcomes for patients suffering from a wide variety disabling life-threatening conditions, particularly cancer.

Язык: Английский

Bisecting GlcNAc modification of vesicular GAS6 regulates CAFs activation and breast cancer metastasis DOI Creative Commons
Jing Li, Xueting Ren, Lin Cao

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 22, 2025

Cancer-associated fibroblasts (CAFs) are a pivotal component of the tumor microenvironment (TME), playing key roles in initiation, metastasis, and chemoresistance. While glycosylation is known to regulate various cellular processes, its impact on CAFs activation remains insufficiently explored. We assessed correlation between bisecting GlcNAc levels markers (α-SMA, PDGFRA, PDGFRB) breast cancer tissues. The effects small extracellular vesicles (sEVs) derived from MDA-MB-231/OEvec MDA-MB-231/OEMGAT3 cells were examined using western blotting, transwell, collagen contraction assays. Proteomic analysis was performed identify dysregulated proteins sEVs different cell lines. role GAS6 validated through vitro vivo experiments. modification expression function analyzed protein degradation N-glycosylation site mutation. effect activated metastasis evaluated blotting transwell found that low associated with within TME cancer. Breast cancer-derived stimulated conversion normal CAFs, by interacting AXL receptors fibroblasts. Introducing into induced their which enhanced metastasis. Notably, decorated GlcNAc, promoted donor cells, leading reduced attenuating GAS6-mediated activation. Taken together, our findings provide new insights functional

Язык: Английский

Процитировано

0
Realizing the promise of ‘La Dolce Vita’ via chemical biology: glycan‐motif editing of sLeX for precision cancer therapeutics DOI Creative Commons
Barbara Richichi, Robert Sackstein

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

The convergence of glycochemistry and glycobiology is enabling the creation new therapeutic approaches with unprecedented capacity to alter cell organismic biology using strategies that can uniquely specifically custom-modify expression key surface glycan motifs. We define this evolving field chemical as 'glycan-motif editing', one principal targets glycoengineering effort sialofucosylated terminal lactosaminyl known sLeX (CD15s). This tetrasaccharide structure plays pivotal roles in both steady-state malignant hematopoiesis, regulation immune response, cancer metastasis. Within biological framework, we discuss immense potential glycan-motif editing precision therapeutics will profoundly improve outcomes for patients suffering from a wide variety disabling life-threatening conditions, particularly cancer.

Язык: Английский

Процитировано

0