Sunday, August 16, 2009

Cancer and Wnt signaling

We've discussed the Wnt signaling pathway several times before, most extensively here. The pathway involves a variety of proteins and their corresponding genes.

Wnt signaling is especially important in embryonic development. In fact, the name is derived from the name of a gene in fruit files that, when mutated, results in wingless flies.

Wnt signaling is also important in stem cells (see here, here, here). As a special case, Wnt is involved in cancer stem cells (see here).

It is far from clear that cancer stem cells are an important factor in many types of cancer. But it appears that Wnt signaling does sometimes play a role itself. Wnt has been found to assist metastasis of colon cancer, and new research suggests it also helps lung cancer to spread quickly to bones and the brain.

Research reveals what drives lung cancer's spread (7/2/09)
Researchers discovered that the same cellular pathway that has been shown to be involved with the spread of colorectal cancer is also responsible for providing lung cancer with an enhanced ability to infiltrate and colonize other organs without delay and with little need to adapt to its new environment. This is a dramatic departure from other cancers, like breast cancer, in which recurrences tend to emerge following years of remission, suggesting that such cancer cells initially lack - and need time to acquire - the characteristics and ability to spread to other organs.

The investigators hypothesized that because not all lung tumors have spread before diagnosis and removal, metastasis may depend on some added feature beyond the mutations that initiate these tumors.

Researchers used bioinformatics to interrogate large collections of lung tumor samples. They found that the WNT cell-signaling pathway was the only one out of the six pathways tested that was hyperactive in lung tumors that went on to metastasize and was normal in those that did not spread. They also observed that WNT hyperactivity was associated with aggressive biological tumor characteristics and poor clinical outcome, suggesting that cancer metastasis is linked to poor survival.

Other research groups, only a few months ago, had found evidence of Wnt involvement in a type of brain cancer, though not one due to metastasis from another location.

Study finds biological clue in brain tumour development (3/18/09)
Clinician -scientists at the University's Children's Brain Tumour Research Centre, working on behalf of the Children's Cancer and Leukaemia Group (CCLG), have studied the role of the WNT biological pathway in central nervous system primitive neuroectodermal tumours (CNS PNET), a type of brain tumour that predominantly occurs in children and presently has a very poor prognosis.

In a paper published in the British Journal of Cancer, they have shown that in over one-third of cases, the pathway is 'activated', suggesting that it plays a role in tumour development. The research also highlighted a link between WNT pathway activation and patient survival — patients who had a CNS PNET tumour that was activated survived for longer than those without pathway activation.

The reason for the link between WNT pathway activation and better patient prognosis is as yet unclear. It could be that these tumours represent a less aggressive subset or that pathway activation itself actually harms the tumour.

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