Dr. Catherine Denicourt
The University of Texas Health Science Center at Houston
Department of Integrative Biology and Pharmacology
- Cell cycle regulation and cancer
- Cyclin and cyclin-dependent kinases
- Oncogenes and tumor suppressors
- Cell migration and metastasis
The G1 phase of the cell cycle is a critical period during which cells decide whether to proliferate or stay quiescent, depending on molecular checkpoints. Human tumors frequently have alterations in cell cycle regulators that normally control progression through G1. Therefore, understanding how deregulated G1 cell cycle signaling pathways lead to tumor progression and metastasis is critical for the design of advanced therapeutic strategies. One of our research interests is to study the role of p27kip1 in cell migration and metastasis. p27Kip1 is a Cdk Inhibitor (CKI) that localizes to the nucleus of normal healthy cells. However, p27Kip1 is often found relocalized to the cytoplasm in some aggressive, metastatic malignancies such as breast cancer. We demonstrated that in the cytoplasm, p27kip1 induces cell migration and promotes metastasis. Our goal is to elucidate the mechanism by which cytoplasmic p27kip1 regulates these processes during breast cancer progression.
We are also studying the interconnection between cell growth and cell division during the G1/S progression of the mammalian cell cycle. Cell growth and division are two highly coordinated processes where a cell must reach a critical size before division can occur. Studies in the budding yeast S. cerevisiae revealed that a critical cell size or “check-point” is required for progression through Start, the equivalent of the mammalian Restriction point in late G1. Cell growth requires an increase in the production of ribosomes to carry out protein synthesis necessary for this increase in cell mass. Pathways controlling various aspects of ribosome biogenesis have recently been linked to cell cycle regulation and cell-size control. Moreover, many proteins often found deregulated in cancer have been linked to ribosome biogenesis suggesting that they could be key therapeutic targets in the treatment of this disease.
Our laboratory utilizes both in vitro and in vivo approaches to dissect out how deregulated cell cycle signaling pathways lead to cancer. A tutorial in my laboratory would provide experience in basic Cell and Molecular Biology techniques as well as in mouse models of metastasis and 3D cultures of breast epithelial cells.
Denicourt C, Saenz CC, Datnow B, Cui XC, and Dowdy SF. Relocalized p27Kip1 Tumor Suppressor Functions as a Cytoplasmic Metastatic Oncogene in Melanoma. Cancer Res. 67:9238-9243 (2007).
Denicourt C, and Dowdy SF. Cip/Kip proteins: more than just CDKs inhibitors. Genes & Dev. 18:851-855 (2004).