Exploring the Relationship between Sall2 and Cancer Growth

Drs. Pincheira, Donner, and Warren have identified a novel factor called Sall2 that binds cell surface receptors for nerve growth factor.  Sall2 appears to act at the cell surface to coordinate the activities of the nerve growth factor receptors and within the nucleus of the cell to regulate gene expression.  The genes affected by Sall2 play an important role in regulating the development of neurons, most particularly in the development and extension of neurites from developing neurons.  Thus, collaborative efforts with members of the Department of Neurology are underway to understand the mechanisms through which Sall2 plays a positive regulatory role in the development of the nervous system, and possibly in neurodegenerative pathologies. 

As mechanisms that regulate neurite extension are similar to those used by cancer cells to spread, to metastasize, Drs. Pincheira, Donner and Warren investigated whether Sall2 might play a role in the initiation, growth, or spread of human colon cancer.  Remarkably, strong evidence suggests that Sall2 may play a role promoting the resistance of cancer cells to chemo- and radiation therapies and may predict whether colon cancer is likely to recur after surgery.  

We have found that Sall2 activates genes that encode survival proteins, thus rendering cancers particularly resistant to therapies.  This observation suggests that cancers may be rendered sensitive to efforts to kill them by suppressing Sall2 expression.  Efforts in this direction are ongoing. 

We have also found that expression of variant forms of Sall2 in human metastatic colon cancer samples recovered from our surgeries increases the likelihood the cancer will recur.  This observation has led members of the Surgical Oncology Research Laboratory to initiate studies of how these Sall2 variants, called single nucleotide polymorphisms or SNPs, may function within the complex environment of human cancer.