Cancer cells exploit eIF4E2-directed translation to enhance their proliferation, migration and invasion

Thumbnail Image
Varga, Joseph
Journal Title
Journal ISSN
Volume Title
University of Guelph

Despite the diversity found in the genetic makeup of cancer, many cancers share the same tumor microenvironment. Hypoxia, an aspect of the tumor microenvironment, causes the suppression of the primary translational machinery. Hypoxic cells switch from using the eukaryotic initiation factor 4E (eIF4E) to using a homologue of eIF4E (eIF4E2), in order to initiate the translation of select mRNAs. This thesis investigates the role of eIF4E2-directed translation in a panel of cancer cell lines during autonomous proliferation, migration and invasion. In this thesis, we show that silencing eIF4E2 abrogates the autonomous proliferation of colon carcinoma. Silencing eIF4E2 in glioblastoma cells resulted in decreased migration and invasion. Furthermore, we link eIF4E2-directed translation of cadherin 22 with the hypoxic migration of glioblastoma. These findings answer questions regarding the biology of cancer and expand the current knowledge of genes exploited during tumor progression. This data also highlights eIF4E2 as a potential therapeutic target.

eIF4E2, CDH22, Cadherin 22, Eukaryotic Translation Initiation Factor 4E Family Member 2, Translation, Hypoxia, Protein, Oxygen, Cancer, Tumor Biology, Invasion, Migration, Autonomous Proliferation, Cell adhesion