Gene controlling melanoma spread identified

Wednesday December 21, 2011

Researchers have identified a gene in melanoma that can dramatically regulate metastases, according to a media release featuring a recent study published in Cancer Cell. According to release, the researchers found that the status of the gene, beta catenin, can specify the extent and location of metastases.

Excerpts of the release are as follows:

Beta catenin is mutated in 5-10% of melanoma, but the significance of this mutation was not previously apparent. The authors showed that the effects of beta catenin mutation are strongly dependent on what other mutations were also present; the combination of specific mutations with beta catenin led to disease metastasis.

Despite the clear importance of metastasis in lives of cancer patients, not much is known about exactly how it happens. The research team’s approach has been to develop new models of cancer formation based on the changes seen in human melanoma. In this case, mutation of beta catenin had dramatic effects on metastasis, but only in certain contexts.

By modulating beta catenin levels in a mouse model of melanoma, the researchers demonstrated that beta catenin is a central mediator of melanoma metastasis to the lymph nodes, lungs, intestine, and spleen. When beta catenin was inactivated in mouse model melanomas, tumour formation was delayed, survival was extended and metastasis was nearly eliminated. These data demonstrate the requirement for beta catenin in melanoma formation and progression.

According to one of the study authors, “we are excited that this new model has advanced the field, as it is an example of a gene the both enhances metastasis when activated and dramatically reduces metastasis when inactivated. There is still much work to be done to see exactly how this happens. We are also encouraged that the model may also be useful to test and evaluate promising new melanoma therapies.”

Sources:

Yale Cancer Center media release:
http://yalecancercenter.org/news/latestnews.aspx#!id=0173691

Damsky WE, Curley DP, Santhanakrishnan M, et al. Beta-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas. Cancer Cell.
Volume 20, Issue 6, 13 December 2011, Pages 741-754. doi:10.1016/j.ccr.2011.10.030
http://www.sciencedirect.com/science/article/pii/S1535610811004053