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Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive the migration, invasion and adhesion of breast cancer and glioma cells

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Title: Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive the migration, invasion and adhesion of breast cancer and glioma cells
Author: Kelly, Nicole J.
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Uniacke, Jim
Abstract: Low oxygen tension (hypoxia) is a common characteristic among cancers that plays a critical role in malignant progression and resistance to therapy. Hypoxia induces changes in gene expression through mechanisms such as the hypoxia inducible factor transcription program and a switch in translation initiation machinery. Hypoxic cells switch from the canonical eukaryotic initiation factor (eIF) 4E to eIF4E2-directed cap-dependent translation. Cancer cells exploit this mechanism to promote many cancer-driven processes, including migration, invasion and cell-cell adhesion. In this study, we demonstrate that the cell-cell adhesion molecule, cadherin-22, is upregulated in hypoxia in an eIF4E2-dependent manner, while E-cadherin translation is repressed in hypoxia. We highlight cadherin-22 as a hypoxia specific driver of cell migration, invasion and adhesion. We also demonstrate that cadherin-22 colocalizes with hypoxia in an in vitro multicellular tumor model and in human glioma and invasive ductal breast carcinoma specimens. By characterizing the role of eIF4E2 and cadherin-22 in cancer, this project will enhance our understanding of tumor biology and offer compelling targets for future therapeutic interventions.
URI: http://hdl.handle.net/10214/11398
Date: 2017-07-26


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