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Thesis
Glycosylation regulates CADM1 tumor suppressive function
Master of Science (M.S.), Drexel University
Aug 2020
DOI:
https://doi.org/10.17918/00000299
Abstract
Melanoma is the deadliest form of skin cancer and incidence is on the rise. While in situ melanoma can be surgically resected with little clinical follow-up, melanoma patients with metastasized disease have poor prognosis. Cell adhesion molecules play a critical role in metastatic progression and recently, our group found levels of the cell adhesion molecule 1 (CADM1) are inversely-correlated with invasiveness and migratory potential of melanoma cells. CADM1 is a single transmembrane protein belonging to the immunoglobulin superfamily and is heavily glycosylated. There are six known N-glycosylation sites in the Ig-like domains of CADM1, some of which can be a substrate for polysialylation - a post-translational modification of chained sialic acid moieties added to asparagine (N) residues. The goal of this project is to determine how glycosylation regulates the anti-metastatic functions of CADM1. In this study, we created human melanoma cell lines designed to inducibly express CADM1 point mutants that swap the reported glycosylated asparagine residues to non-modifiable glutamine (Q). Western blotting reveals that these mutants are lower molecular weight than wild type CADM1, suggesting that each site is modified. To assess the biological role of these glycosylation, melanoma cell lines were subjected to Boyden chamber-based migration and invasion assays as well as collagen sprouting. We found that disruption of N-linked glycosylation at N113 largely inhibited the anti-migratory/invasive effects of CADM1. We plan to build on these studies; investigating the activity and regulation of putative CADM1 glycotransferases, potentially defining a novel prognostic indicator and an innovative therapeutic avenue for metastatic melanoma patients.
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Details
- Title
- Glycosylation regulates CADM1 tumor suppressive function
- Creators
- Zongguan Huang
- Contributors
- Jacqueline M. Barker (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 53 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991014695135304721