Deranged Function of Tumor Suppressor Proteins

Tumor suppressor proteins are the brakes that impede the deregulated and inappropriate cell growth found in cancer.  Under the leadership of Dr. Warren, members of the Surgical Oncology Research Laboratory have been scanning the genome of human metastatic colon cancer samples, and other malignancies as well, in order to identify lesions arising from mutated or inappropriately expressed tumor suppressors. 

A particularly interesting tumor suppressor is Mig-6, which inhibits signaling events induced by activated receptor protein tyrosine kinases.  In a study of papillary thyroid cancer, Dr. Warren and his colleagues found that high expression of Mig-6 was associated with longer survival and favorable outcomes, thus showing that Mig-6 acts as a tumor suppressor protein in thyroid cancers. 

Investigation of Mig-6 was extended to specimens of human metastatic colon cancer.  Surprisingly, in this malignancy high expression of Mig-6 was associated with poor outcome.  Two explanations for this result are under investigation: firstly, evaluation of the Mig-6 gene in colon cancer samples has led to the detection of mutant, and possibly non-functional, forms of the gene; and secondly, the expression of Mig-6 is driven by oncogenic events that may be operative within tumors.  Thus, elevated Mig-6 expression may be reflective of a particularly aggressive tumor microenvironment.  This latter possibility suggests that Mig-6 may function as a sentinel or biomarker that can identify colon cancers predisposed to rapid growth and/or spread. 

Identifying biomarkers that can predict whether cancers are likely to recur or assume an aggressive phenotype is one of the goals of the Surgical Oncology Research Laboratory.   With such biomarkers in hand we aim to individualize and personalize the treatments we offer to every patient.