Researchers find important 'target' playing role in tobacco-related lung cancers

February 9, 2012

Researchers at Moffitt Cancer Center in Tampa, Fla., have discovered that the immune response regulator IKBKE (serine/threonine kinase) plays two roles in tobacco-related non-small cell lung cancers. Tobacco carcinogens induce IKBKE and, in turn, IKBKE induces chemotherapy resistance.

The study was published in a recent issue of Oconogene.

"IKBKE is a newly identified oconogene, a gene linked to cancer," said study lead author Jin Q. Cheng, Ph.D., M.D., who studies and their in cancer. "In our study, we demonstrated that IKBKE is a STAT 3 target gene and is induced by tobacco. is a signaling and transcription gene that is activated in various types of cancer and is required for ."

As a "transcription factor" STAT3 plays a key role in many cellular processes, such as cell growth and , or "apoptosis."

"It has been well documented that STAT3 is activated by growth factors and environmental carcinogenesis, such as nicotine," said Cheng. "STAT3 directly binds to the IKBKE promoter and induces IKBKE transcription."

Tobacco smoke is the strongest documented tumor initiator and promoter in lung cancer. The underlying molecular mechanism is still largely unknown.

"IKBKE is induced by tobacco carcinogens and mediates tobacco action in promoting lung cancer cell survival," said Cheng. "Armed with this knowledge, interventions targeting the IKBKE pathway could be developed."

Cheng and his colleagues found that when STAT3 induces IKBKE expression, IKBKE's expression induces chemotherapy resistance. Conversely, "knocking down" IKBKE sensitizes cells to chemotherapy, suggesting that there is a therapeutic role for targeting IKBKE.

While IKBKE has been found to be "over expressed" in ovarian, breast and , in this study IKBKE has for the first time been associated with non-small cell lung cancer in patients with a history of tobacco use, and particularly by tobacco's nicotine component. The researchers stated that upon exposure to nicotine, cells express high levels of IKBKE protein. In their study co-expression of STAT3 and IKBKE was "observed in primary non-small cell lung cancer."

"Current treatments for non-small cell lung cancer include surgery, radiotherapy and chemotherapy," explained Cheng. "Advanced patients generally develop chemotherapy and radiotherapy resistance, so there is a great need to understand the molecular mechanism of therapy resistance in order to find 'targets' to overcome resistance."

The discovery that STAT3 appears to regulate IKBKE in response to nicotine induced by tobacco carcinogen may also help develop a strategy for an intervention in non-small cell lung cancer by targeting IKBKE.

Explore further: Researchers find more clues to causes of breast cancer

Related Stories

Researchers find more clues to causes of breast cancer

October 27, 2011
Publishing in the current issue of The Journal of Biological Chemistry (Vol. 286, No 43), researchers at Moffitt Cancer Center in Tampa, Fla., have discovered additional mechanisms of "Akt" activation and suggest a component ...

'DIMming' cancer growth -- STAT: Diindolylmethane suppresses ovarian cancer

January 26, 2012
Ovarian cancer is a major cause of death worldwide. Approximately 25,000 women will be diagnosed with ovarian cancer this year and 15,000 women will die from it in the United States alone. The novel anti-cancer drug diindolylmethane ...

Combination drug therapy urged to battle lung cancer

February 2, 2012
Combination drug therapy may be needed to combat non-small cell lung cancer (NSCLC), according to a study by the Translational Genomics Research Institute (TGen) and Van Andel Research Institute (VARI).

TGen presents lung cancer studies at Amsterdam conference

July 7, 2011
The Translational Genomics Research Institute (TGen) is presenting two key studies, including one today, at the 14th World Conference on Lung Cancer, July 3-7 in Amsterdam.

Recommended for you

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.