Long-chain glucosylceramides crosstalk with LYN mediates endometrial cell migration

Dulani Wimalachandra, Wimalachandra D, Joan Xiaohui Yang, Yang JX, Zhu L, Lina Zhu, Evan Tan, Harry Asada, H. Harry Asada, Asada H, Jerry Kok Yen Chan, Jerry Y K Chan, Yie Hou Lee, Lee YH
Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017 · vol. 1863(1) , pp. 71–80 · doi:10.1016/j.bbalip.2017.10.002 · PMID:29050963 · W2767159615
article OA: closed CC0 ⤵ 6 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-06 ⓘ

This paper investigates how long-chain glucosylceramides interact with LYN kinase to influence endometrial cell migration.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Endometriosis is a disease characterized by regurgitated lesions which are invasive and migratory, embedding at ectopic, extra-uterine locations. Extracellular glucosylceramides (GlcCers), bioactive sphingolipids potentiating signals for cell migration, are found in elevated levels in endometriosis; however underlying mechanisms that result in cellular migration are poorly defined. Here, we demonstrated that internalized GlcCer induced migratory activity in immortalized human endometrial stromal cells (HESCs), with highest potency observed in long-chain GlcCer. Long-chain ceramide (Cer) similarly induced cellular migration and mass spectrometry results revealed that the migratory behavior was contributed through glycosylation of ceramides. Cells treated with GlcCer synthase inhibitor, or RNAi-mediated knockdown of glucosylceramide synthase (GCS), the enzyme catalyzing GlcCer production attenuated cell motility. Mechanistic studies showed that GlcCer acts through stromal cell-derived factor-1 alpha and its receptor, CXC chemokine receptor 4 (SDF-1α-CXCR4) signaling axis and is dependent on phosphorylation of LYN kinase at Tyr396, and dephosphorylation of Tyr507. Migration was prominently attenuated in cells exposed to CXCR4 antagonist, AMD3100, yet can be rescued with diprotin A, which prevents the degradation of SDF-1α. Furthermore, blocking of LYN kinase activity in the presence of SDF-1α and GlcCer reduced HESC migration, suggesting that LYN acts downstream of GlcCer-SDF-1α-CXCR4 axis as part of its intracellular signal transduction. Our results reveal a novel role of long-chain GlcCer and the dialog between GlcCer, LYNpTyr396 and SDF-1α-CXCR4 in inducing HESC migration. This finding may improve our understanding how endometriotic lesions invade to their ectopic sites, and the possibility of using GlcCer to modulate the SDF-1α-CXCR4-LYNpTyr396 axis in endometriosis.

My notes (saved in your browser only)

MeSH descriptors

Cell Movement Endometrium Endometrium Glucosylceramides src-Family Kinases Cell Movement Cell Movement Cells, Cultured Endometrium Endometrium Female Glucosylceramides Glucosylceramides Glucosylceramides Humans Receptor Cross-Talk Receptor Cross-Talk Receptor Cross-Talk Signal Transduction Signal Transduction

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (66)

Cited by (7)

Source provenance

europepmc
last seen: 2026-08-17T06:11:01.428247+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:20:13.663096+00:00
License: CC0 · commercial use OK