# Dietary palmitic acid inhibits colorectal cancer progression through enhancing bisecting GlcNAc
**Authors:** Lei Lei, Juan Tang, Yuejiao Lv, Bingyi Jia, Wenqing Cai, Shuangshuang Sheng, Keying Li, Zhiwen Shi, Ning Fan, Zengqi Tan, Xiang Li, Feng Guan
PMC · DOI: 10.1172/jci.insight.179533 · JCI Insight · 2026-03-23
## TL;DR
Dietary palmitic acid slows colorectal cancer by boosting a specific sugar modification on a protein called desmoglein 2.
## Contribution
This study reveals a direct mechanism linking dietary palmitic acid to reduced colorectal cancer progression via bisecting GlcNAc modification.
## Key findings
- Dietary palmitic acid inhibits CRC carcinogenesis by increasing bisecting GlcNAc levels.
- Bisecting GlcNAc modification on desmoglein 2 suppresses CRC through the EGFR/AKT pathway.
- Mice lacking Mgat3 do not benefit from a palmitic acid-rich diet in CRC prevention.
## Abstract
Glycosylation changes are pivotal in colorectal cancer (CRC) development. The role of bisecting GlcNAc, a specific N-glycosylation type catalyzed by glycosyltransferase MGAT3, in CRC progression remains elusive. Previous studies indicated that dietary interventions can be beneficial for patients with certain congenital disorders of glycosylation. However, the impact of dietary fatty acids, such as palmitic acid (PA), on glycosylation regulation remains largely unclear. Here, we observed markedly decreased levels of bisecting GlcNAc and MGAT3 in colonic tissues of CRC patients. Downregulation of bisecting GlcNAc in CRC cells increased cell proliferation, migration, and invasion, while decreasing apoptosis. Moreover, a PA-rich diet inhibited CRC carcinogenesis in azoxymethane/dextran sodium sulfate–induced CRC mice by elevating bisecting GlcNAc levels. However, in Mgat3fl/fl Villin-Cre mice the inhibitory effects of the PA-rich diet were abolished. Intact glycopeptide analysis revealed that PA enhanced the bisecting GlcNAc modification on desmoglein 2 (DSG2). Additionally, DSG2 was identified to inhibit CRC carcinogenesis through the EGFR/AKT signaling pathway. In conclusion, dietary PA suppresses CRC carcinogenesis by regulating bisecting GlcNAc modification on DSG2, providing a direct mechanistic link between dietary fatty acids and CRC.
Dietary palmitic acid suppresses CRC progression by enhancing bisecting GlcNAc modification on desmoglein 2, providing a direct mechanistic link between dietary fatty acids and CRC.
## Linked entities
- **Genes:** MGAT3 (beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase) [NCBI Gene 4248], DSG2 (desmoglein 2) [NCBI Gene 1829], EGFR (epidermal growth factor receptor) [NCBI Gene 1956], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207]
- **Proteins:** MGAT3 (beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase), DSG2 (desmoglein 2)
- **Chemicals:** palmitic acid (PubChem CID 985)
- **Diseases:** colorectal cancer (MONDO:0005575)
## Full-text entities
- **Genes:** Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], MGAT3 (beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase) [NCBI Gene 4248] {aka GNT-III, GNT3}, Lamp1 (lysosomal-associated membrane protein 1) [NCBI Gene 16783] {aka CD107a, LGP-120, LGP-A, Lamp-1, P2B, Perk}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Vil1 (villin 1) [NCBI Gene 22349] {aka Vil}, Pcna (proliferating cell nuclear antigen) [NCBI Gene 18538], Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, MGAT4A (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) [NCBI Gene 11320] {aka GNT-IV, GNT-IVA, GnT-4a}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, EEA1 (early endosome antigen 1) [NCBI Gene 8411] {aka MST105, MSTP105, ZFYVE2}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, Pomgnt2 (protein O-linked mannose beta 1,4-N-acetylglucosaminyltransferase 2) [NCBI Gene 215494] {aka Ago61, Gtdc2}, LAMP2 (lysosome associated membrane protein 2) [NCBI Gene 3920] {aka CD107b, DND, LAMP-2, LAMPB, LGP-96, LGP110}, Dsg2 (desmoglein 2) [NCBI Gene 13511] {aka D18Ertd293e}, DSG2 (desmoglein 2) [NCBI Gene 1829] {aka CDHF5, HDGC}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Mgat3 (mannoside acetylglucosaminyltransferase 3) [NCBI Gene 17309] {aka 1110038J12Rik, GnT-III}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}
- **Diseases:** MCAM (MESH:D008545), lung adenocarcinoma (MESH:D000077192), Cancer (MESH:D009369), Crohn disease (MESH:D003424), colitis (MESH:D003092), breast cancer (MESH:D001943), colon tumor (MESH:D003110), myelodysplastic syndrome (MESH:D009190), colonic inflammation (MESH:D007249), colonic (MESH:D003108), uterine corpus endometrial carcinoma (MESH:D016889), BRCA (MESH:D001941), lung cancer (MESH:D008175), carcinogenesis (MESH:D063646), congenital disorders of glycosylation (MESH:D018981), metastasis (MESH:D009362), esophageal cancer (MESH:D004938), stomach adenocarcinoma (MESH:D013274), bladder cancer (MESH:D001749), cardiovascular disease (MESH:D002318), pancreatic and gallbladder cancers (MESH:D010190), deficiency of the (MESH:D007153), para-carcinoma (MESH:D002277), CRC (MESH:D015179)
- **Chemicals:** CHX (MESH:D003513), PUFA (MESH:D005231), acetonitrile (MESH:C032159), Glycopeptide (MESH:D006020), PA (MESH:D019308), GlcNAc (MESH:D000117), DMSO (MESH:D004121), H&E (MESH:D006371), IAM (MESH:D007460), oleic acid (MESH:D019301), Chlo (MESH:D002738), urea (MESH:D014508), glucose (MESH:D005947), DTT (MESH:D004229), linoleic acid (MESH:D019787), polybrene (MESH:D006583), Bisecting GlcNAc (-), TFA (MESH:D014269), MUFAs (MESH:D005229), EdU (MESH:C022811), SFAs (MESH:D005227), CCK-8 (MESH:D012844), MG132 (MESH:C072553), AOM (MESH:D001397), hygromycin (MESH:C026273), fat (MESH:D005223), OA (MESH:D019319), LA (MESH:D007811)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), AIN-93 — Homo sapiens (Human), Nephropathic cystinosis, Finite cell line (CVCL_CW96), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), NCM460 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0460), pancreatic beta — Mesocricetus auratus (Golden hamster), Hamster pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_5M15)
## Full text
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## Figures
8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13043105/full.md
## References
46 references — full list in the complete paper: https://tomesphere.com/paper/PMC13043105/full.md
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Source: https://tomesphere.com/paper/PMC13043105