Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During malignancy, perturbed O-glycosylation confers global influence on cancer progression. As a hallmark of cancer metastasis, GalNAc-type O-glycosylation initiation is aberrantly raised, but the regulatory mechanism is still mysterious. Here, we show that LAMTOR5 raises abnormal initiation of O-glycosylation in breast cancer metastasis. LAMTOR5 was highly expressed in adenocarcinoma and correlated with Tn antigen, a product of O-glycosylation initiation, in both clinical metastatic breast cancer specimens and secondary metastasis mouse model. LAMTOR5-modulated O-glycosylation initiating enzyme GALNT1 conferred Tn accumulation and predicted poor survival. Mechanistically, LAMTOR5 stimulated transcriptions of GALNT1 through coactivating c-Jun, and triggered dislocation of GALNT1 in the endoplasmic reticulum (ER) via LAMTOR5 dependent-activation of c-Src. This unusual initiation of O-glycosylation resulted in the abundance of Tn modified glycoproteins, such as MUC1 and OPN. Collectively, our findings indicate that LAMTOR5/c-Jun/c-Src axis serves as the upstream regulator of abnormal O-glycosylation initiation and potential therapeutic targets in breast cancer metastasis.
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PMID:LAMTOR5 raises abnormal initiation of O-glycosylation in breast cancer metastasis via modulating GALNT1 activity. 3183 47