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Health and Medicine

Researchers Discover A Novel Gene That Stops Cancer Spreading

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Justine Alford

Guest Author

clockJul 21 2014, 09:45 UTC
1553 Researchers Discover A Novel Gene That Stops Cancer Spreading
Salk Institute for Biological Studies. Focal adhesion complexes (green) are usually large and sticky, anchoring a cell into place (left). When the gene DIXDC1 is knocked out, complexes instead become small and numerous (right), assisting cancer spread.

Researchers at the Salk Institute have discovered a new gene that plays a crucial role in a biochemical pathway that prevents cancer cells from escaping the initial site of tumor growth and spreading round the body. It is hoped that this novel information could help identify patients that are more likely to respond to new therapies that target other parts of this pathway. The study has been published in Molecular Cell.

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Certain types of cancer are more likely to spread to other parts of the body, or metastasize, than others. Some lung cancers are particularly renowned for their aggressive nature and ability to spread rapidly and early on, meaning that survival is often poor. In fact, the five-year survival rate of patients with lung cancer, which does not only affect smokers, is as low as 10% which is considerably lower than that of breast or prostate cancer which is greater than 80%.

“The reason behind why some tumors do that [metastasize] and others don’t has not been very well understood,” said lead researcher Reuben Shaw in a news-release. “Now, through this work, we are beginning to understand why some subsets of lung cancer are so invasive.”

In order for tumor cells to break away from the primary site and elope to other body parts via the circulatory system, they have to override cellular processes that are designed to keep them in place. It is known that cancer cells can alter the expression of molecules, or focal adhesion complexes, that anchor cells to surfaces.

It is also known that around 20% of lung cancers have an altered anticancer, or tumor suppressor, gene known as LKB1. These cancers are known to be particularly aggressive; however, prior to this research, links between this gene and focal adhesions had not been identified.

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In this study, the researchers identified a new gene called DIXDC1 which forms part of a signaling pathway that ultimately suppresses metastasis. The DIXDC1 gene product is directed, by LKB1, to localize to focal adhesions where it can then regulate the size and number of structures that hold the cell in place.

When DIXDC1 is switched on, a small number of large adhesions are produced that anchor the cell to a particular surface. When it is interfered with in certain tumor cells, however, many smaller adhesions are produced that help make the cell mobile. This can either occur by direct inhibition of DIXDC1 or through loss of the LKB1 gene.

“The communication between LKB1 and DIXDC1 is responsible for a ‘stay-put’ signal in cells,” said lead author Jonathan Goodwin.

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The researchers then demonstrated that overexpressing DIXDC1 in tumor cells with low levels of this gene dampened their metastatic ability in vitro and in vivo. This was particularly surprising given the number of proteins under the control of LKB1.

While there are currently no specific treatments for cancers with these particular alterations, the researchers say that these patients may benefit from novel treatments that target the focal adhesions, which are currently going through clinical trials. The research therefore aids the identification of patients that are likely to respond to such therapies. 


Health and Medicine
  • cancer,

  • lung cancer,

  • metastasis

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