Effects of PTEN localization and phosphatase activity on gene expression profiling of glioblastoma cells
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AbstractPTEN possesses both protein and lipid phosphatase activities, with its tumor-suppressor function mainly depends on its lipid phosphatase activity through inhibiting the PI3K/AKT signaling pathway at the cell membrane. However, increasing evidence have demonstrated that PTEN also localizes to other intracellular organelles such as the endoplasmic reticulum, the mitochondria, or the nucleus where it plays important roles in multiple cellular processes. To further understand how PTEN localization affects the gene expression profiling in cancer cells, a PTEN null glioblastoma cell line, U87MG, was stably expressing wild-type, nuclear localization signal (NLS)-tagged, nuclear export signal (NES)-tagged and myristoylation (MYR)-tagged PTEN.

Ion Torrent based whole transcriptome sequencing was used for gene expression analysis. Gene ontology enrichment analysis showed that the most common cellular component regulated by PTEN over-expression was extracellular factors, which function as growth factor-binding or fibronectin-binding molecules related to cell adhesion or organ system development. In contrast, nuclear PTEN promoted the enrichment of genes in collagen-binding and integrin-binding, which may be related to blood vessel development or cell motility. KEGG pathway enrichment also confirmed that PTEN over-expression upregulated focal adhesion pathway, an important pathway that frequently disrupted in PTEN Hamartoma Tumor Syndrome (PHTS). Moreover, nuclear PTEN differentially regulated genes showed higher enrichment in immune response signaling pathways.

This unique gene expression profiling driven by NLS-PTEN indicated that besides the phosphatase activities, nuclear PTEN may have additional functions than merely inhibiting the PI3K signaling pathway. The transcriptome data showed potential downstream targets of PTEN in different subcellular localizations, which may lead to unique biological functions. More functional studies will be carried out to further validate how intracellular PTEN regulates the expression of these genes, and what are the signaling pathways involved in the regulatory processes.

Funding sources – This work was supported by the Hong Kong PhD Fellowship (PF12-13876) to WY. AC was supported by a General Research Fund grant (#460713), a Collaborative Research Fund grant (C014-14G) from the Hong Kong University Grants Committee, a Lo Kwee-Seong Biomedical Research Seed Fund, and the Brain & Mind Institute.
All Author(s) ListWang Yubing, Chan Man Lok Andrew
Name of ConferenceAmerican Association for Cancer Research Annual Meeting 2017
Start Date of Conference01/04/2017
End Date of Conference05/04/2017
Place of ConferenceWashington, DC
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

Last updated on 2018-22-01 at 12:49