Binhua P. Zhou, M.D., Ph.D.
Assistant Professor
Pharmacology & Toxicology
email:  bpzhou@utmb.edu

Metastasis, the spread of cells from a primary tumor to distant sites, is the main cause of death in patients with cancer. Our long-term goal is to eliminate the incidence of cancer metastasis by understanding the molecular mechanism underlying the initial step of metastasis. The metastatic process remains incompletely characterized at the molecular and biochemical levels because metastasis is a “hidden” event that takes place inside the body and is difficult to examine. This process is believed to consist of four distinct steps that require the coordinated actions of multiple genes: invasion, intravasation, extravasation, and metastatic colonization. Using in vivo video microscopy, the initial step, the acquisition of invasive ability and motility and extracellular matrix proteolysis, culminating in the shedding of cells into the circulation either directly or via the lymphatics, is the rate-limiting step in the metastatic cascade. Beyond this step, survival of cells in the circulation, their arrest in a distant organ, and their initial extravasation are relatively efficient processes. Epithelial-mesenchymal transition (EMT), a process vital for morphogenesis during embryonic development, is attracting increasing attention from oncologists as a potential mechanism for the initial step of metastasis. Many genes implicated in EMT during embryogenesis are being discovered, one after another, to control metastasis. We are currently focusing on characterization of the functional role and regulation of Snail/Slug transcription factors in the control of EMT. Snail is a zinc-finger transcriptional repressor that was identified in Drosophila as a suppressor of the transcription of shotgun (an E-cadherin homologue) in the control of embryogenesis. Flies and mice without Snail are lethal because of severe defects at the gastrula stage during development. Expression of Snail correlates with the tumor grade and nodal metastasis of many types of tumor and predicts a poor outcome in patients with metastatic cancer. We recently found that Snail is highly unstable with a short half-life of only about 25 minutes and the activity of Snail is mainly regulated by the stability of the protein and its cellular location. We are employing biochemical, molecular, and cellular approaches to study the functional regulation of Snail in breast cancer and will apply the knowledge that we gained for the prevention, diagnosis, and treatment of metastatic breast cancer in a long run. The goal of our research program is to uncover altered signaling pathways that regulate metastasis in cancer and, by discovery these pathways, to identify molecules that may serve as the therapeutic targets for metastasis prevention.