Description:

It is known that primary solid tumors are generally not the cause of cancer-related deaths but that 80-90% of mortality is the result of cancer cells gaining the ability to leave the primary tumor, activate survival processes, invade surrounding tissues, intravasate into the circulation, extravasate into new tissues, and form secondary tumors, often after long latencies. We have discovered that distinct ERK substrate recognition domains make major contributions to specific cancer phenotypes such as proliferation versus metastatic progression. While much is known regarding ERK proliferative signaling mechanisms, much less is understood regarding the role of ERK signaling in the acquisition of metastatic properties. Therefore, defining the signaling mechanisms and biological outcomes downstream of ERK that contribute to the development of metastasis are of critical importance. To discover new processes linked to the initiation and establishment of the metastatic phenotype, we have completed several large-scale screening efforts (gene expression arrays, proteomics, phosphoproteomics, and metabolomics) aimed at mapping the temporal changes that occur during ERK2-driven acquisition of aggressive, mesenchymal phenotypes. These approaches have yielded several new discoveries such as mechanisms of cross-talk between ERK2 and TGFb pathways, chromatin remodeling through regulation of histone chaperones, metabolic reprogramming and identification of metabolites acting as second messengers that drive aging-associated metastasis. How ERK2 and TGFb contribute to chromatin remodeling and metabolic reprogramming will be discussed.

John Blenis, PhD
Anna Maria and Stephen Kellen Professor of Cancer Research
Professor, Department of Pharmacology
Associate Director of Basic Science, Sandra and Edward Meyer Cancer Center
Weill Cornell Medicine