Biomedical Sciences Research Seminar

TG2 in Prostate Cancer, What role?

Atomic structure of a biological molecule
Seminars

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Grace Adeola Atobatele, NTU presents: TG2 in Prostate Cancer, What role?

  • From: Wednesday 10 October 2018, 1 pm
  • To: Wednesday 10 October 2018, 2 pm
  • Location: 282, Erasmus Darwin, Nottingham Trent University, Clifton Campus, Clifton Lane, Nottingham, NG11 8NS

Past event

Event details

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Grace Adeola Atobatele, NTU presents: TG2 in Prostate Cancer, What role?

Abstract

The majority of prostate cancer (PCa)-related deaths are due to the advanced stage of the disease; bone metastasis and involvement of soft tissue accounts for most treatment failure. With most of the current treatment having little effect on long-term survival, the need to identify new biomarkers for either prevention or/and personalised therapy cannot be overemphasized. Transglutaminase-2(TG2) is a multifunctional enzyme that catalyzes calcium-dependent post-translational modification of proteins, particularly those of the extracellular matrix leading to their stabilisation and accumulation. Aberrant expression/activity of TG2 has been linked to cancer progression via promotion of cell survival and growth, increased cell migration, invasion and metastatic potential of several cancer cell lines. Alternative TG2 transcripts have been reported to be more expressed in PCa cell lines compared to canonical TG2, however the contribution of canonical TG2 and TG2 alternative transcripts to cancer progression has been poorly characterised. Here, we focus on investigating the expression and role of TG2 and its main truncated isoform (TGM2_v2) in the aggressiveness of metastatic prostate cancer. To explore whether TG2 alternative transcript TGM2_v2 contributes to the growth advantage of cells in solid tumours, firstly we knock out TG2 gene in the well characterised metastatic cell line, PC3. Six stable clones of PC3 cells with TG2 knockout (KO) were established employing CRISPR-Cas9 gene editing. Then the effect of TG2 gene deficiency on transcriptomics of cancer progression genes was determined by digital expression profiling via the nCounter analyser (NanoString technology) in the five TG2KO clones and four control clones. Overall, data revealed increased expression of genes in the extracellular matrix (ECM) structure and remodelling category highlighting the involvement of TG2 with ECM homeostasis. Genes with decreased expression in the TG2 KO PC 3 clones were involved in epithelial mesenchymal transition (EMT) and extracellular matrix layers. Furthermore TG2KO affected proliferation, cell migration and cell attachment of PC3 cells, suggesting a contribution of TG2 to the malignant phenotype.
The transcriptome elicited by both full length and truncated TG2 variant, was explored in a similar way in PC3 TG2 KO clones transfected back with individual variants (TGM2_v1 and TGM2_v2). Add back of either TGM2_v1 or TGM2_v2 restored the expression of most cancer progression genes which had been affected by TG2 KO. TGM2_v2 was able to independently regulate cancer progression genes in a similar manner to full length TGM2, suggesting that this variant might alone contribute to the overall effect recorded by TGM2 in prostate cancer progression.

This seminar is hosted by Dr Eli Verderio - Edwards and Dr Stephanie McArdle

All welcome.

For any enquiries please contact Dr John Dickenson

Location details

Room/Building:

282, Erasmus Darwin

Address:

Nottingham Trent University
Clifton Campus
Clifton Lane
Nottingham
NG11 8NS

Past event

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