Type

Journal Article

Authors

Ann M Hopkins
Ivan R Nabi
Arnold D K Hill
Lee D Hazelwood
Irina S Babina
Simona Donatello

Subjects

Biochemistry

Topics
cancer cells breast cancer cell interaction association caveolin 1 cell migration lipid rafts cancer cell

Lipid Raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration. (2011)

Abstract Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Ann M Hopkins, Ivan R Nabi, Arnold D K Hill, Lee D Hazelwood, Irina S Babina, Simona Donatello

Experts in our system

1
Ann M Hopkins
Royal College of Surgeons in Ireland
Total Publications: 26
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110