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'Master activator' gene for cancer spread found

8 May 2018
Appeared in BioNews 948

A gene that plays a major role in promoting metastasis – the spread of cancer around the body – has been identified. 

The research, published in Nature Cell Biology, found that the protein produced by the gene PSPC1, which is present at very low levels in normal cells, is upregulated in 60 to 70 percent of aggressive cancers. Due to its interaction with many other factors promoting the spread of cancers, the researchers have identified the PSPC1 gene as a 'master activator' for metastasis.

The protein was found at elevated levels in samples from patients with breast, liver, lung and prostate cancer. Higher levels of the PSPC1 protein was associated with reduced patient survival. 

In the early stages of cancer, tumours are mostly confined to a single part of the body. Later, the cancer can spread, or metastasise, becoming more aggressive. At this stage, cancer cells move throughout the body via blood vessels. The researchers showed that PSPC1 has a key role in promoting metastasis, hijacking a normal growth-control mechanism, known as the TGF-1-beta signalling pathway.

As a result, upregulating the gene helps cancerous cells invade blood cells, move around the body, grow faster and survive longer. Higher levels of the PSPC1 protein also promoted resistance to drugs to treat the cancers. 

'In elucidating PSPC1 functionality and TGF-beta 1 behaviour in metastasising cancer, this research represents a major breakthrough,' Dr Yuh-Shan Jou of the Academia Sinica's Institute of Biomedical Sciences, lead author on the study, told the Taipei Times

The authors speculate that PSPC1 could be used as a drug target in future; their results suggest that metastasis could be prevented by inhibiting PSPC1 activity. 

Dr Jou said that the research team had identified an inhibitor of PSPC1 with potential medical value, although actual applications remain far in the future. In the nearer term, the authors say that the overexpression of PSPC1 could be used as a biomarker to help predict patient response to certain drugs. 

Paraspeckle factor turns TGF-β1 pro-metastatic
Nature Cell Biology |  28 March 2018
PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis
Nature Cell Biology |  28 March 2018
Taiwanese scientists isolate gene that spurs spread of cancer
Taiwan News |  3 May 2018
Team makes cancer breakthrough
Taipei Times |  3 May 2018
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