Title : Expression level and glycan dynamics determine the net effects of
TIMP-1 on cancer progression
Abstract :
- Tissue inhibitor of metalloproteinases ( TIMPs; TIMP-1, -2, -3 and -4 ) are endogenous inhibitor for matrix metalloproteinases ( MMPs ) that are responsible for remodeling the extracellular matrix ( ECM ) and involved in migration, invasion and metastasis of tumor cells
- Unlike under normal conditions, the imbalance between MMPs and TIMPs is associated with various diseased states
- Among TIMPs, TIMP-1 , a 184-residue protein , is the only N-linked glycoprotein with glycosylation sites at N30 and N78
- The structural analysis of the catalytic domain of human stromelysin-1 ( MMP-3 ) and human TIMP-1 suggests new possibilities of the role of TIMP-1 glycan moieties as a tuner for the proteolytic activities by MMPs
- Because the TIMP-1 glycosylation participate in the interaction, aberrant glycosylation of TIMP-1 presumably affects the interaction, thereby leading to pathogenic dysfunction in cancer cells
- TIMP-1 has not only the cell proliferation activities but also anti-oncogenic properties
- Cancer cells appear to utilize these bilateral aspects of TIMP-1 for cancer progression; an elevated TIMP-1 level exerts to cancer development via MMP-independent pathway during the early phase of tumor formation, whereas it is the aberrant glycosylation of TIMP-1 that overcome the high anti-proteolytic burden
- The aberrant glycosylation of TIMP-1 can thus be used as staging and/or prognostic biomarker in colon cancer
Output (sent_index, trigger,
protein,
sugar,
site):
- 3. glycoprotein, , TIMP-1, -, -
- 3. glycoprotein, , glycoprotein, -, -
- 3. glycosylation, , -, -, sites
- 5. glycosylation, , TIMP-1, -, -
- 7. glycosylation, , TIMP-1, -, -
- 8. glycosylation, , TIMP-1, -, -
Output(Part-Of) (sent_index,
protein,
site):
- 3. TIMP-1, N30 and N78
- 3. glycoprotein, N30 and N78
- 3. glycoprotein, sites
- 4. TIMP-1, domain
- 4. stromelysin-1, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):