Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

Planells-Palop, Vicente, Hazazi, Ali, Feichtinger, Julia, Jezkova, Jana, Thallinger, Gerhard, Alsiwiehri, Naif O., Almutairi, Mikhlid, Parry, Lee ORCID: https://orcid.org/0000-0002-4467-9196, Wakeman, Jane A. and McFarlane, Ramsay J. 2017. Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. Molecular Cancer 16 , 84. 10.1186/s12943-017-0653-4

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview

Abstract

Background: Cancer/testis(CT)geneshaveexpressionnormallyrestrictedtothetestis,butbecomeactivatedduring oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined. Methods: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types. Results: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/ self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types. Conclusions: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Publisher:	BioMed Central
ISSN:	1476-4598
Date of First Compliant Deposit:	28 April 2017
Date of Acceptance:	18 April 2017
Last Modified:	04 May 2023 04:12
URI:	https://orca.cardiff.ac.uk/id/eprint/100179

Citation Data

Cited 14 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item