Cbx7 is epigenetically silenced in glioblastoma and inhibits cell migration by targeting YAP/TAZ-dependent transcription

Nawaz, Zahid and Patil, Vikas and Arora, Anjali and Hegde, Alangar S and Arivazhagan, Arimappamagan and Santosh, Vani and Somasundaram, Kumaravel (2016) Cbx7 is epigenetically silenced in glioblastoma and inhibits cell migration by targeting YAP/TAZ-dependent transcription. In: SCIENTIFIC REPORTS, 6 .

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Abstract

Glioblastomas (GBM) are the most malignant form of astrocytomas which are difficult to treat and portend a grave clinical course and poor prognosis. In this study, we identified Chromobox homolog 7 (Cbx7), a member of Polycomb Repressive Complex 1 (PRC1), as a downregulated gene in GBM owing to its promoter hypermethylation. Bisulphite sequencing and methylation inhibitor treatment established the hypermethylation of Cbx7 in GBM. Exogenous overexpression of Cbx7 induced cell death, inhibited cell proliferation, colony formation and migration/invasion of the glioma cells. GSEA of Cbx7 regulated genes identified Cbx7 as a repressor of transcription co- activators YAP/TAZ, the inhibitory targets of the Hippo signalling pathway. In good correlation, the exogenous expression of Cbx7 repressed the YAP/TAZ- dependent transcription and downregulated CTGF, a bonafide YAP/TAZ target. We also observed reduced levels of phospho-JNK in Cbx7 expressing cells. Additionally, CTGF silencing and pharmacological inhibition of JNK also inhibited glioma cell migration. Further, Cbx7 failed to inhibit cell migration significantly in the presence of exogenously overexpressed CTGF or constitutively active JNK. Thus, our study identifies Cbx7 as an inhibitor of glioma cell migration through its inhibitory effect on YAP/TAZ-CTGF-JNK signalling axis and underscores the importance of epigenetic inactivation of Cbx7 in gliomagenesis.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Publisher:	NATURE PUBLISHING GROUP
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	05 Jul 2016 06:23
Last Modified:	05 Jul 2016 06:23
URI:	http://eprints.iisc.ac.in/id/eprint/54130

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