Cancer/testis (CT) genes have
expression normally restricted to the testis, but become activated during
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
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.
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.
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.