Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04626 (
erbB-2
)
5,251
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition.
Carcinoembryonic antigen-related cell adhesion molecule 6
(
CEACAM6
), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of
CEACAM6
glycosylation has not been addressed in cancers. We recently developed an anti-
CEACAM6
Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated
CEACAM6
compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated
CEACAM6
was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients.
CEACAM6
promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with
epidermal growth factor (EGF) receptor
(EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn
256
(N256) of
CEACAM6
. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in
CEACAM6
-overexpressing cells. In conclusion, the complex N-glycosylation of
CEACAM6
is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated
CEACAM6
with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.
...
PMID:Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation. 2889 50
