Journal
CANCER LETTERS
Volume 429, Issue -, Pages 54-65Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.04.040
Keywords
YKL-40; PTEN; PI3K; JAK2/STAT3; Transcriptomes
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Funding
- Lo Kwee-Seong Biomedical Research Seed Fund [6903806]
- Collaborative Research Fund grant from the Hong Kong University Grants Committee [C4014-14G]
- Pilot Project Fund from the Brain and Mind Institute of the Chinese University of Hong Kong [4930742]
- Hong Kong PhD Fellowship [PF12-13584, PF12-13876]
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Constitutive activation of the phosphoinositide 3-kinase/AKT signaling pathway is frequently observed in high-grade gliomas with high frequency of losing PTEN tumor suppressor. To identify transcriptomic profiles associated with a hyperactivated PI3K pathway, RNA-sequencing analysis was performed in a glioblastoma cell line stably expressing PTEN. RNA-sequencing revealed enriched transcripts of pro-inflammatory mediators, and among the genes that displayed high differential expression was the secreted glycoprotein YKL-40. Treatment with chemical inhibitors that target the PI3K/AKT pathway elicited differential effects on YKL-40 expression in selected GBM cell lines, indicating that its expression displayed tumor cell-specific variations. This variability appeared to be correlated with the ability to transactivate the immune signaling molecules JAK2 and STAT3. In summary, the differential expression of the immunomodulatory molecule YKL-40 may affect the treatment efficacy of PI3K/AKT-based pathway inhibitors in glioblastoma.
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