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Study Reveals the Causes of Cancer by Environmental Stress

by VR Sreeraman on Nov 6 2007 4:59 PM

Environmental stress causes cancer by reducing the activity level of an enzyme that causes cell death, say researchers led by Indian researcher Kapil Bhalla and Dr. Yonghua Yang.

The study was conducted at the University of South Florida in the laboratory of Dr Bhalla, director of the MCG Cancer Centre.

The researchers found that stress-inducing agents, such as oxidative stress, recruited a protein called SENP1 that removed a regulator called SUMO1 away from the enzyme SIRT1 so that its activity level drops.

SIRT1, found throughout the body, is a regulator of protein function through a process called acetylation.

Yang said that increased SIRT1 activity, which was routinely present in cancer, even made cancer cells more resistant to anticancer drugs such as chemotherapy.

Yang added that the complication was decreasing programmed cell death, or apoptosis increased longevity.

“Whether apoptosis is good or bad depends on the circumstances. But it’s good for cancer therapy,” Yang said.

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The team said that the study described as to how stress caused desumoylation and sumoylation of SIRT1 and ultimately caused cancer.

“This paper describes how stress causes desumoylation and sumoylation of SIRT1 and ultimately cancer,” the researchers said.

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Bhalla said that stress-inducing agents produced the association of the enzyme, SIRT-1, with the desumoylating enzyme, SENP1, so that cells became more resistant to stress-induced apoptosis.

“Stress-inducing agents produce the association of this enzyme, SIRT-1, with the desumoylating enzyme, SENP1, so cells become more resistant to stress-induced apoptosis,” Bhalla said.

“Once SIRT1 is desumoylated, it’s less active and you want its activity. When SIRT1 is less active, p53, a tumour suppressor gene that also causes apoptosis, becomes more active,” he added.

Yang said that the finding about the relationship between stress and cancer opened the door for treatments that increased SENP1 activity, making it easier for cells that were becoming cancerous, to die.

“This is one of the things that makes cancer cells so durable, one way they survive so well. We want to see if we can block that process and make cells die,” he said. The study is published in Nature Cell Biology.

Source-ANI
SRM/C


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